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Archive for the ‘NK Cell-Based Cancer Immunotherapy’ Category


2018 Nobel Prize in Physiology or Medicine for contributions to Cancer Immunotherapy to James P. Allison, Ph.D., of the University of Texas, M.D. Anderson Cancer Center, Houston, Texas. Dr. Allison shares the prize with Tasuku Honjo, M.D., Ph.D., of Kyoto University Institute, Japan

Reporter: Aviva Lev-Ari, PhD, RN

 

See

Immune System Stimulants: Articles of Note @pharmaceuticalintelligence.com

Curators: Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/05/01/immune-system-stimulants-articles-of-note-pharmaceuticalintelligence-com/

 

Immune-Oncology Molecules In Development & Articles on Topic in @pharmaceuticalintelligence.com

Curators: Stephen J Williams, PhD and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/01/11/articles-on-immune-oncology-molecules-in-development-pharmaceuticalintelligence-com/

 

 

Monday, October 1, 2018

NIH grantees win 2018 Nobel Prize in Physiology or Medicine.

The 2018 Nobel Prize in Physiology or Medicine has been awarded to National Institutes of Health grantee James P. Allison, Ph.D., of the University of Texas, M.D. Anderson Cancer Center, Houston, Texas. Dr. Allison shares the prize with Tasuku Honjo, M.D., Ph.D., of Kyoto University Institute, Japan, for their discovery of cancer therapy by inhibition of negative immune regulation.

The Royal Swedish Academy of Sciences said, “by stimulating the inherent ability of our immune system to attack tumor cells this year’s Nobel Laureates have established an entirely new principle for cancer therapy.”

Dr. Allison discovered that a particular protein (CTLA-4) acts as a braking system, preventing full activation of the immune system when a cancer is emerging. By delivering an antibody that blocks that protein, Allison showed the brakes could be released. The discovery has led to important developments in cancer drugs called checkpoint inhibitors and dramatic responses to previously untreatable cancers. Dr. Honjo discovered a protein on immune cells and revealed that it also operates as a brake, but with a different mechanism of action.

“Jim’s work was pivotal for cancer therapy by enlisting our own immune systems to launch an attack on cancer and arrest its development,” said NIH Director Francis S. Collins, M.D., Ph.D. “NIH is proud to have supported this groundbreaking research.”

Dr. Allison has received continuous funding from NIH since 1979, receiving more than $13.7 million primarily from NIH’s National Cancer Institute (NCI) and National Institute of Allergy and Infectious Diseases (NIAID).

“This work has led to remarkably effective, sometime curative, therapy for patients with advanced cancer, who we were previously unable to help,” said NCI Director Ned Sharpless, M.D. “Their findings have ushered in the era of cancer immunotherapy, which along with surgery, radiation and cytotoxic chemotherapy, represents a ‘fourth modality’ for treating cancer. A further understanding of the biology underlying the immune system and cancer has the potential to help many more patients.”

“Dr. Allison’s elegant and groundbreaking work in basic immunology over four decades and its important applicability to cancer is a vivid demonstration of the critical nature of interdisciplinary biomedical research supported by NIH,” says NIAID Director Anthony S. Fauci, M.D.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

SOURCE

https://www.nih.gov/news-events/news-releases/nih-grantees-win-2018-nobel-prize-physiology-or-medicine

 

Dr. Lev-Ari covered in person the following curated articles about James Allison, PhD since his days at University of California, Berkeley, including the prizes awarded prior to the 2018 Nobel Prize in Physiology.

 

2018 Albany Medical Center Prize in Medicine and Biomedical Research goes to NIH’s Dr. Rosenberg and fellow immunotherapy researchers James P. Allison, Ph.D., and Carl H. June, M.D.

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/08/15/2018-albany-medical-center-prize-in-medicine-and-biomedical-research-goes-to-nihs-dr-rosenberg-and-fellow-immunotherapy-researchers-james-p-allison-ph-d-and-carl-h-june-m-d/

 

Lectures by The 2017 Award Recipients of Warren Alpert Foundation Prize in Cancer Immunology, October 5, 2017, HMS, 77 Louis Paster, Boston

REAL TIME Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/09/08/lectures-by-the-2017-award-recipients-of-warren-alpert-foundation-prize-in-cancer-immunology-october-5-2017-hms-77-louis-paster-boston/

 

Cancer-free after immunotherapy treatment: Treating advanced colon cancer – targeting KRAS gene mutation by tumor-infiltrating lymphocytes (TILs) and Killer T-cells (NK)

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/12/08/cancer-free-after-immunotherapy-treatment-treating-advanced-colon-cancer-targeting-kras-gene-mutation-by-tumor-infiltrating-lymphocytes-tils-and-killer-t-cells-nk/

 

New Class of Immune System Stimulants: Cyclic Di-Nucleotides (CDN): Shrink Tumors and bolster Vaccines, re-arm the Immune System’s Natural Killer Cells, which attack Cancer Cells and Virus-infected Cells

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/04/24/new-class-of-immune-system-stimulants-cyclic-di-nucleotides-cdn-shrink-tumors-and-bolster-vaccines-re-arm-the-immune-systems-natural-killer-cells-which-attack-cancer-cells-and-virus-inf/

 

UC Berkeley research led to Nobel Prize-winning immunotherapy

Immunologist James P. Allison today shared the 2018 Nobel Prize in Physiology or Medicine for groundbreaking work he conducted on cancer immunotherapy at UC Berkeley during his 20 years as director of the campus’s Cancer Research Laboratory.

James Allison

James Allison, who for 20 years was a UC Berkeley immunologist conducting fundamental research on cancer, is now at the M.D. Anderson Cancer Center in Houston, Texas.

Now at the University of Texas M.D. Anderson Cancer Center in Houston, Allison shared the award with Tasuku Honjo of Kyoto University in Japan “for their discovery of cancer therapy by inhibition of negative immune regulation.”

Allison, 70, conducted basic research on how the immune system – in particular, a cell called a T cell – fights infection. His discoveries led to a fundamentally new strategy for treating malignancies that unleashes the immune system to kill cancer cells. A monoclonal antibody therapy he pioneered was approved by the Food and Drug Administration in 2011 to treat malignant melanoma, and spawned several related therapies now being used against lung, prostate and other cancers.

“Because this approach targets immune cells rather than specific tumors, it holds great promise to thwart diverse cancers,” the Lasker Foundation wrote when it awarded Allison its 2015 Lasker-DeBakey Clinical Medical Research Award.

Allison’s work has already benefited thousands of people with advanced melanoma, a disease that used to be invariably fatal within a year or so of diagnosis. The therapy he conceived has resulted in elimination of cancer in a significant fraction of patients for a decade and counting, and it appears likely that many of these people are cured.

“Targeted therapies don’t cure cancer, but immunotherapy is curative, which is why many consider it the biggest advance in a generation,” Allison said in a 2015 interview. “Clearly, immunotherapy now has taken its place along with surgery, chemotherapy and radiation as a reliable and objective way to treat cancer.”

“We are thrilled to see Jim’s work recognized by the Nobel Committee,” said Russell Vance, the current director of the Cancer Research Laboratory and a UC Berkeley professor of molecular and cell biology. “We congratulate him on this highly deserved honor. This award is a testament to the incredible impact that the fundamental research Jim conducted at Berkeley has had on the lives of cancer patients”

“I don’t know if I could have accomplished this work anywhere else than Berkeley,” Allison said. “There were a lot of smart people to work with, and it felt like we could do almost anything. I always tell people that it was one of the happiest times of my life, with the academic environment, the enthusiasm, the students, the faculty.”

In this video about UC Berkeley’s new Immunotherapeutics and Vaccine Research Initiative (IVRI), Allison discusses his groundbreaking work on cancer immunotherapy.

In fact, Allison was instrumental in creating the research environment of the current Department of Molecular and Cell Biology at UC Berkeley as well as the department’s division of immunology, in which he served stints as chair and division head during his time at Berkeley, said David Raulet, director of Berkeley’s Immunotherapeutics and Vaccine Research Initiative (IVRI).

“His actions helped create the superb research environment here, which is so conducive to making the fundamental discoveries that will be the basis of the next generation of medical breakthroughs,” Raulet said.

Self vs. non-self

Allison joined the UC Berkeley faculty as a professor of molecular and cell biology and director of the Cancer Research Laboratory in 1985. An immunologist with a Ph.D. from the University of Texas, Austin, he focused on a type of immune system cell called the T cell or T lymphocyte, which plays a key role in fighting off bacterial and viral infections as well as cancer.

Supercharging the immune system to cure disease: immunotherapy research at UC Berkeley. (UC Berkeley video by Roxanne Makasdjian and Stephen McNally)

At the time, most doctors and scientists believed that the immune system could not be exploited to fight cancer, because cancer cells look too much like the body’s own cells, and any attack against cancer cells would risk killing normal cells and creating serious side effects.

“The community of cancer biologists was not convinced that you could even use the immune system to alter cancer’s outcome, because cancer was too much like self,” said Matthew “Max” Krummel, who was a graduate student and postdoctoral fellow with Allison in the 1990s and is now a professor of pathology and a member of the joint immunology group at UCSF. “The dogma at the time was, ‘Don’t even bother.’ ”

“What was heady about the moment was that we didn’t really listen to the dogma, we just did it,” Krummel added. Allison, in particular, was a bit “irreverent, but in a productive way. He didn’t suffer fools easily.” This attitude rubbed off on the team.

Trying everything they could in mice to tweak the immune system, Krummel and Allison soon found that a protein receptor called CTLA-4 seemed to be holding T cells back, like a brake in a car.

Postdoctoral fellow Dana Leach then stepped in to see if blocking the receptor would unleash the immune system to actually attack a cancerous tumor. In a landmark paper published in Science in 1996, Allison, Leach and Krummel showed not only that antibodies against CTLA-4 released the brake and allowed the immune system to attack the tumors, but that the technique was effective enough to result in long-term disappearance of the tumors.

“When Dana showed me the results, I was really surprised,” Allison said. “It wasn’t that the anti-CTLA-4 antibodies slowed the tumors down. The tumors went away.”

After Allison himself replicated the experiment, “that’s when I said, OK, we’ve got something here.”

Checkpoint blockade

The discovery led to a concept called “checkpoint blockade.” This holds that the immune system has many checkpoints designed to prevent it from attacking the body’s own cells, which can lead to autoimmune disease. As a result, while attempts to rev up the immune system are like stepping on the gas, they won’t be effective unless you also release the brakes.

Allison in 1993

James Allison in 1993, when he was conducting research at UC Berkeley on a promising immunotherapy now reaching fruition. (Jane Scherr photo)

“The temporary activation of the immune system though ‘checkpoint blockade’ provides a window of opportunity during which the immune system is mobilized to attack and eliminate tumors,” Vance said.

Allison spent the next few years amassing data in mice to show that anti-CTLA-4 antibodies work, and then, in collaboration with a biotech firm called Medarex, developed human antibodies that showed promise in early clinical trials against melanoma and other cancers. The therapy was acquired by Bristol-Myers Squibb in 2011 and approved by the FDA as ipilimumab (trade name Yervoy), which is now used to treat skin cancers that have metastasized or that cannot be removed surgically.

Meanwhile, Allison left UC Berkeley in 2004 for Memorial Sloan Kettering research center in New York to be closer to the drug companies shepherding his therapy through clinical trials, and to explore in more detail how checkpoint blockade works.

“Berkeley was my favorite place, and if I could have stayed there, I would have,” he said. “But my research got to the point where all the animal work showed that checkpoint blockade had a lot of potential in people, and working with patients at Berkeley wasn’t possible. There’s no hospital, no patients.”

Thanks to Allison’s doggedness, anti-CTLA-4 therapy is now an accepted therapy for cancer and it opened the floodgates for a slew of new immunotherapies, Krummel said. There now are several hundred ongoing clinical trials involving monoclonal antibodies to one or more receptors that inhibit T cell activity, sometimes combined with lower doses of standard chemotherapy.

Antibodies against one such receptor, PD-1, which Honjo discovered in 1992, have given especially impressive results. Allison’s initial findings can be credited for prompting researchers, including Allison himself, to carry out the studies that have demonstrated the potent anti-cancer effects of PD-1 antibodies. In 2015, the FDA approved anti-PD-1 therapy for malignant melanoma, and has since approved it for non-small-cell lung, gastric and several other cancers.

Science magazine named cancer immunotherapy its breakthrough of 2013 because that year, “clinical trials … cemented its potential in patients and swayed even the skeptics. The field hums with stories of lives extended: the woman with a grapefruit-size tumor in her lung from melanoma, alive and healthy 13 years later; the 6-year-old near death from leukemia, now in third grade and in remission; the man with metastatic kidney cancer whose disease continued fading away even after treatment stopped.”

Allison pursued more clinical trials for immunotherapy at Sloan-Kettering and then in 2012 returned to his native Texas.

Born in Alice, Texas, on Aug. 7, 1948, Allison earned a B.S. in microbiology in 1969 and a Ph.D. in biological science in 1973 from the University of Texas, Austin.

RELATED INFORMATION

SOURCE

http://news.berkeley.edu/2018/10/01/uc-berkeley-research-led-to-nobel-prize-winning-immunotherapy/

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Lectures by The 2017 Award Recipients of Warren Alpert Foundation Prize in Cancer Immunology, October 5, 2017, HMS, 77 Louis Paster, Boston

Reporter: Aviva Lev-Ari, PhD, RN

Top, from left: James Allison and Lieping Chen. Bottom, from left: Gordon Freeman, Tasuku Honjo (NOT ATTENDED), Arlene Sharpe.

Aviva Lev-Ari, PhD, RN was in attendance and covered this event LIVE

 

The 2017 Warren Alpert Foundation Prize has been awarded to five scientists for transformative discoveries in the field of cancer immunology.

Collectively, their work has elucidated foundational mechanisms in cancer’s ability to evade immune recognition and, in doing so, has profoundly altered the understanding of disease development and treatment. Their discoveries have led to the development of effective immune therapies for several types of cancer.

The 2017 award recipients are:

  • James Allison, professor of immunology and chair of the Department of Immunology, The University of Texas MD Anderson Cancer Center – Immune checkpoint blockage in Cancer Therapy strictly Genomics based drug
  1. 2017 FDA approved a genomics based drug
  2. and co-stimulatory signals
  3. CTLA-4 blockade, CD28, AntiCTLA-4 induces regression of Transplantable Murine tumor
  4. enhance tumor-specific immune response
  5. Fully antibody human immune response in 10,000 patients – FDA approved 2011
  6. Metastatic melanoma – 3 years survival, programmed tumor death, PD-1, MHC-A1
  7. Ipi/Nivo vs. Ipi – combination – 60% survival vs Ipi alone
  8. Anti CTA4 vs Anti-PD-1
  9. responsive T cell population – MC38 TILs
  10. MC38 Infiltrating T cell populations: T-reg, CD4, Effector, CD8, NKT/gamma-delta
  11. Checkpoint blockage modulates infiltrating T cell population frequencies
  12. T reg correlated with Tumor growth
  13. Combination therapy lead to CURE survival at 80% rate vs CTAL-4 40% positive outcome

Not Attended — Tasuku Honjo, professor of immunology and genomic medicine, Kyoto University – Immune regulation of Cancer Therapy by PD-1 Blockade

 

  • Lieping Chen, United Technologies Corporation Professor in Cancer Research and Professor of immunobiology, of dermatology and of medicine, Yale University – Adoptive Resistance: Molecular Pathway t Cancer Therapy – focus on solid tumors
  1. Enhancement – Enhance normal immune system – Co-stimulation/Co-inhibition Treg, and Cytokines, adoptive cell therapy, Lymphoid organs stores
  2. Normalization – to correct defective immune system – normalizing tumor immunity, diverse tumor escape mechanisms
  3. Anti-PD therapy: regression of large solid tumors: normalizing tumor immunity targeting tumor microenvironment: Heterogeneity, functional modulation, cellular and molecular components – classification by LACK of inflamation, adaptive resistance, other inhibitory pathways, intrinsic induction
  4. avoid autoimmune toxicity,
  5. Resetting immune response (melanoma)
  6. Understad Resistance: Target missing resistance or Adaptive resistance Type II= acquired immunity
  • Gordon Freeman, professor of medicine, Dana-Farber Cancer Institute, Harvard Medical School – PD-L1/PD-1 Cancer Immunotherapy
  1. B7 antibody
  2. block pathway – checkpoint blockage, Expand the T cells after recognition of the disease. T cell receptor signal, activation, co -stimulatory: B71 molecule, B72 – survival signals and cytokine production,.Increased T cell proliferation,
  3. PDL-1 is a ligand of PD 1. How T cell die? genes – PD1 Gene was highly expressed,
  4. Interferon gamma upregulate PD-L1 expression
  5. Feedback loop Tumor – stimulating immune response, interferon turn off PD1
  6. PD-L1 and PD-L2 Expression: Interferom
  7. Trancefuctor MHC, B7-2
  8. PD-L! sisgnat inhibit T-cell activation: turn off Proliferation and cytokine production — Decreasing the immune response
  9. T cell DNA Content: No S-phase devided cell
  10. PD-L1 engagement of PD-1 results in activation : Pd-1 Pathway inhibits T Cell Actiivation – lyposite motility,
  11. Pd-L2 is a second ligand for PD-1 and inhibits T cell activation
  12. PDl-1 expression: BR CA, Ovarian, Colonol-rectal, tymus, endothelial
  13. Blockage of the Pathway – Immune response enhanced
  14. Dendritic cells express PD-L1, PD-L2 and combination of Two, Combination was best of all by increase of cytokine production, increasing the immune response.
  15. PD-L1 blockade enhanced the immune response , increase killing and increased production of cytokines,
  16. anti-tumor efficacy of anti-PD-1/Pd-L1
  17. Pancreatic and colono-rector — PD-L, PDL1, PDL2 — does not owrkd.
  18. In menaloma: PD-1 works better than CYLA-4
  19. Comparison of Targeted Therapy: BRAF TKI vs Chemo high % but short term
  20. Immunotherapy – applies several mechanism: pre-existing anti-therapy
  21. Immune desert: PD=L does not work for them
  22. COMBINATION THERAPY: BLOCK TUMOR INVASION THEN STIMULATE IMMUNE RESPONSE — IT WILL WORK
  23. PD blockage + nutrients and probiotic
  24. Tumor Genome Therapy
  25. Tumore Immuno-evasion Score
  26. Antigens for immune response – choose the ones
  27. 20PD-1 or PD-L1 drugs in development
  28. WHO WILL THE DRUG WORK FOR?

 

  • Arlene Sharpe, the George Fabyan Professor of Comparative Pathology, Harvard Medical School; senior scientist, department of pathology, Brigham and Women’s Hospital – Multi-faceted Functionsof the PD-1 Pathway
  1. function of the pathway: control T cell activation and function of maintain immune tolerance
  2. protect tissues from damage by immune response
  3. T cell dysfunction during cancer anf viral infection
  4. protection from autoimmunity, inflammation,
  5. Mechanism by which PD-1 pathway inhibits anti-tumor immunity
  6. regulation of memoryT cell responce of PD-1
  7. PD-1 signaling inhibit anti-tumor immunity
  8. Compare: Mice lacking CD8-Cre- (0/5) cleared vs PD-1-/-5/5 – PD-1 DELETION: PARTIAL AND TIMED: DELETION OF PD-1 ON HALF OG TILS STARTING AT DAY 7 POSTTUMOR IMPLANTATION OF BOTH PD-1 AND PD-1 TILS: – Tamoxifen days 7-11
  9. Transcription profile: analysis of CD8+ TILs reveal altered metabolism: Fatty Acid Metabolism vs Oxidative Phosphorylation
  10. DOes metabolic shift: WIld type mouth vs PD-1-/_ P14: analyze Tumor cell killingPD-1-/- enhanced FAO increases CD8+ T cell tocicity
  11. Summary: T cell memory development and PD-1: T effectors vs T cell memory: Primary vs Secondary infection: In the absent of PD-1, CD8+ T cels show increase expansion of T cells
  12. INFLUENZA INFECTION: PRIMARY more virus in lung in PD-1 is lacking
  13. Acute infection: PD-1 controls memory T cell differentiation vs PD-1 increase expansion during effector phase BUT impaired persistence during memory phase: impaired cytokine production post re-challenge
  14. PD-1 immunotherapy work for patients with tumor: Recall Response and Primary response
  15. TIL density Primary vs Long term survivor – 5 days post tumor implantation – rechallenged long term survival
  16. Hot tumor vs Cold tumor – Deletion of PD-1 impairs T memory cell development

 

Opening Remarks: George Q. Daley, MD, PhD, DEAN, HMS

  • Scientific collaboration check point – avoid the body attacking itself, sabotaging the immune system
  • 1987 – Vaccine for HepB
  • Eight of the awardees got the Nobel Prize

 

Moderated by Joan Brugge, PhD, HMS, Prof. of Cell Biology

  • Evolution of concepts of Immunotherapy: William Coley’s Toxin streptoccocus skin infection.
  • 20th century: Immuno-surveilence, Immune response – field was dead in 1978 replaced by Immunotherapy
  • Rosenberg at NIH, high dose of costimulatory molecule prevented tumor reappearanceantbody induce tumor immunity–>> immune theraphy by check point receptor blockade – incidence of tumor in immune compromised mice – transfer T cell
  • T cell defficient, not completely defficient, self recognition of tumor,
  • suppress immmune – immune evasion
  • Michael Atkins, MD, Detupy Director, Georgetown-Lombardi, Comprehensive Cancer Center Clinical applications of Checkpoint inhibitors: Progress and Promise
  1. Overwhelm the Immune system, hide, subvert, Shield, defend-deactivating tumor trgeting T cells that ATTACK the immune system
  2. Immune system to TREAT the cancer
  3. Monotherapy – anti PD1/PD-L1: Antagonist activity
  4. Evading immune response: prostate, colcn
  5. MMR deficiency
  6. Nivolumab in relaped/Refractory HODGKIN LYMPHOMAS – over expression of PD-L1 and PDL2in Lymphomas
  7. 18 month survival better with Duv in Lung cancer stage 3 – anti PD-1- adjuvant therapy with broad effectiveness
  8. Biomarkers for pD-L1 Blockage
  9. ORR higher in PD-L1
  10. Improve Biomarkers: Clonality of T cells in Tumors
  11. T-effector Myeloid Inflammation Low – vs Hogh:
  12. Biomarker Model: Neoantigen burden vs Gene expression vs CD8+
  13. Tissue DIagnostic Labs: Tumor microenveironmenr
  14. Microbiome
  15. Combination: Nivo vs Nivo+Ipi is superior: DETERMINE WHEN TO STOP TREATMENT
  16. 15/16 stopped treatment – Treatment FREE SURVIVAL
  17. Sequencing with Standard Therapies
  18. Brain metastasis – Immune Oncology Therapy – crosses the BBB
  19. Less Toxic regimen, better toxicity management,
  20. Use Immuno therapy TFS
  21. combination – survival must be justified
  22. Goal: to make Cancer a curable disease vs cancer becoming a CHronic disease

 

Closing Remarks: George Q. Daley, MD, PhD, DEAN, HMS

 

The honorees will share a $500,000 prize and will be recognized at a day-long symposium on Oct. 5 at Harvard Medical School.

The Warren Alpert Foundation, in association with Harvard Medical School, honors trailblazing scientists whose work has led to the understanding, prevention, treatment or cure of human disease. The award recognizes seminal discoveries that hold the promise to change our understanding of disease or our ability to treat it.

“The discoveries honored by the Warren Alpert Foundation over the years are remarkable in their scope and potential,” said George Q. Daley, dean of Harvard Medical School. “The work of this year’s recipients is nothing short of breathtaking in its profound impact on medicine. These discoveries have reshaped our understanding of the body’s response to cancer and propelled our ability to treat several forms of this recalcitrant disease.”

The Warren Alpert Foundation Prize is given internationally. To date, the foundation has awarded nearly $4 million to 59 scientists. Since the award’s inception, eight honorees have also received a Nobel Prize.

“We commend these five scientists. Allison, Chen, Freeman, Honjoand Sharpe are indisputable standouts in the field of cancer immunology,” said Bevin Kaplan, director of the Warren Alpert Foundation. “Collectively, they are helping to turn the tide in the global fight against cancer. We couldn’t honor more worthy recipients for the Warren Alpert Foundation Prize.”

The 2017 award: Unraveling the mysterious interplay between cancer and immunity

Understanding how tumor cells sabotage the body’s immune defenses stems from the collective work of many scientists over many years and across multiple institutions.

Each of the five honorees identified key pieces of the puzzle.

The notion that cancer and immunity are closely connected and that a person’s immune defenses can be turned against cancer is at least a century old. However, the definitive proof and demonstration of the steps in this process were outlined through findings made by the five 2017 Warren Alpert prize recipients.

Under normal conditions, so-called checkpoint inhibitor molecules rein in the immune system to ensure that it does not attack the body’s own cells, tissues and organs. Building on each other’s work, the five award recipients demonstrated how this normal self-defense mechanism can be hijacked by tumors as a way to evade immune surveillance and dodge an attack. Subverting this mechanism allows cancer cells to survive and thrive.

A foundational discovery made in the 1980s elucidated the role of a molecule on the surface of T cells, the body’s elite assassins trained to seek, spot and destroy invaders.

A protein called CTLA-4 emerged as a key regulator of T cell behavior—one that signals to T cells the need to retreat from an attack. Experiments in mice lacking CTLA-4 and use of CTLA-4 antibodies demonstrated that absence of CTLA-4 or blocking its activity could lead to T cell activation and tumor destruction.

Subsequent work identified a different protein on the surface of T cells—PD-1—as another key regulator of T cell response. Mice lacking this protein developed an autoimmune disease as a result of aberrant T cell activity and over-inflammation.

Later on, scientists identified a molecule, B7-H1, subsequently renamed PD-L1, which binds to PD-1, clicking like a key in a lock. This was followed by the discovery of a second partner for PD-1—the molecule PD-L2—which also appeared to tame T-cell activity by binding to PD-1.

The identification of these molecules led to a set of studies showing that their presence on human and mouse tumors rendered the tumors resistant to immune eradication.

A series of experiments further elucidated just how tumors exploit the interaction between PD-1 and PD-L1 to survive. Specifically, some tumor cells appeared to express PD-L1, essentially “wrapping” themselves in it to avoid immune recognition and destruction.

Additional work demonstrated that using antibodies to block this interaction disarmed the tumors, rendering them vulnerable to immune destruction.

Collectively, the five scientists’ findings laid the foundation for antibody-based therapies that modulate the function of these molecules as a way to unleash the immune system against cancer cells.

Antibody therapy that targets CTLA-4 is currently approved by the FDA for the treatment of melanoma. PD-1/PD-L1 inhibitors have already shown efficacy in a broad range of cancers and have been approved by the FDA for the treatment of melanoma; kidney; lung; head and neck cancer; bladder cancer; some forms of colorectal cancer; Hodgkin lymphoma and Merkel cell carcinoma.

In their own words

“I am humbled to be included among the illustrious scientists who have been honored by the Warren Alpert Foundation for their contributions to the treatment and cure of human disease in its 30+ year history.  It is also recognition of the many investigators who have labored for decades to realize the promise of the immune system in treating cancer.”
        -James Allison


“The award is a great honor and a wonderful recognition of our work.”
         Lieping Chen



I am thrilled to have made a difference in the lives of cancer patients and to be recognized by fellow scientists for my part in the discovery of the PD-1/PD-L1 and PD-L2 pathway and its role in tumor immune evasion.  I am deeply honored to be a recipient of the Alpert Award and to be recognized for my part in the work that has led to effective cancer immunotherapy. The success of immunotherapy has unleashed the energies of a multitude of scientists to further advance this novel strategy.”
                                        -Gordon Freeman


I am extremely honored to receive the Warren Alpert Foundation Prize. I am very happy that our discovery of PD-1 in 1992 and subsequent 10-year basic research on PD-1 led to its clinical application as a novel cancer immunotherapy. I hope this development will encourage many scientists working in the basic biomedical field.”
-Tasuku Honjo


“I am truly honored to be a recipient of the Alpert Award. It is especially meaningful to be recognized by my colleagues for discoveries that helped define the biology of the CTLA-4 and PD-1 pathways. The clinical translation of our fundamental understanding of these pathways illustrates the value of basic science research, and I hope this inspires other scientists.”
-Arlene Sharpe

Previous winners

Last year’s award went to five scientists who were instrumental in the discovery and development of the CRISPR bacterial defense mechanism as a tool for gene editing. They were RodolpheBarrangou of North Carolina State University, Philippe Horvath of DuPont in Dangé-Saint-Romain, France, Jennifer Doudna of the University of California, Berkeley, Emmanuelle Charpentier of the Max Planck Institute for Infection Biology in Berlin and Umeå University in Sweden, and Virginijus Siksnys of the Institute of Biotechnology at Vilnius University in Lithuania.

Other past recipients include:

  • Tu Youyou of the China Academy of Chinese Medical Science, who went on to receive the 2015 Nobel Prize in Physiology or Medicine with two others, and Ruth and Victor Nussenzweig, of NYU Langone Medical Center, for their pioneering discoveries in chemistry and parasitology of malaria and the translation of their work into the development of drug therapies and an anti-malarial vaccine.
  • Oleh Hornykiewicz of the Medical University of Vienna and the University of Toronto; Roger Nicoll of the University of California, San Francisco; and Solomon Snyder of the Johns Hopkins University School of Medicine for research into neurotransmission and neurodegeneration.
  • David Botstein of Princeton University and Ronald Davis and David Hogness of Stanford University School of Medicine for contributions to the concepts and methods of creating a human genetic map.
  • Alain Carpentier of Hôpital Européen Georges-Pompidou in Paris and Robert Langer of MIT for innovations in bioengineering.
  • Harald zur Hausen and Lutz Gissmann of the German Cancer Research Center in Heidelberg for work on the human papillomavirus (HPV) and cancer of the cervix. Zur Hausenand others were honored with the Nobel Prize in Physiology or Medicine in 2008.

The Warren Alpert Foundation

Each year the Warren Alpert Foundation receives between 30 and 50 nominations from scientific leaders worldwide. Prize recipients are selected by the foundation’s scientific advisory board, which is composed of distinguished biomedical scientists and chaired by the dean of Harvard Medical School.

Warren Alpert (1920-2007), a native of Chelsea, Mass., established the prize in 1987 after reading about the development of a vaccine for hepatitis B. Alpert decided on the spot that he would like to reward such breakthroughs, so he picked up the phone and told the vaccine’s creator, Kenneth Murray of the University of Edinburgh, that he had won a prize. Alpert then set about creating the foundation.

To award subsequent prizes, Alpert asked Daniel Tosteson (1925-2009), then dean of Harvard Medical School, to convene a panel of experts to identify scientists from around the world whose research has had a direct impact on the treatment of disease.

SOURCE

https://hms.harvard.edu/news/warren-alpert-foundation-honors-pioneers-cancer-immunology

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Koch Institute Immune Engineering Symposium on October 16 & 17, 2017, Kresge, MIT

Reporter: Aviva Lev-Ari, PhD, RN

 

Koch Institute Immune Engineering Symposium on October 16 & 17, 2017.

 

Summary: Biological, chemical, and materials engineers are engaged at the forefront of immunology research. At their disposal is an analytical toolkit honed to solve problems in the petrochemical and materials industries, which share the presence of complex reaction networks, and convective and diffusive molecular transport. Powerful synthetic capabilities have also been crafted: binding proteins can be engineered with effectively arbitrary specificity and affinity, and multifunctional nanoparticles and gels have been designed to interact in highly specific fashions with cells and tissues. Fearless pursuit of knowledge and solutions across disciplinary boundaries characterizes this nascent discipline of immune engineering, synergizing with immunologists and clinicians to put immunotherapy into practice.

SPEAKERS:

Michael Birnbaum – MIT, Koch Institute

Arup Chakraborty – MIT, Insititute for Medical Engineering & Sciences

Jianzhu Chen – MIT, Koch Institute

Jennifer R. Cochran – Stanford University

Jennifer Elisseeff – Johns Hopkins University

K. Christopher Garcia – Stanford University

George Georgiou – University of Texas at Austin

Darrell Irvine – MIT, Koch Institute

Tyler Jacks – MIT, Koch Institute

Doug Lauffenburger – MIT, Biological Engineering and Koch Institute

Wendell Lim – University of California, San Francisco

Harvey Lodish – Whitehead Institute and Koch Institute

Marcela Maus – Massachusetts General Hospital

Garry P. Nolan – Stanford University

Sai Reddy – ETH Zurich

Nicholas Restifo – National Cancer Institute

William Schief – The Scripps Research Institute

Stefani Spranger – MIT, Koch Institute

Susan Napier Thomas – Georgia Institute of Technology

Laura Walker – Adimab, LLC

Jennifer Wargo – MD Anderson Cancer Center

Dane Wittrup – MIT, Koch Institute

Kai Wucherpfennig – Dana-Farber Cancer Institute

Please contact ki-events@mit.edu with any questions.

SOURCE

From: Koch Institute Immune Engineering Symposium <ki-events@mit.edu>

Reply-To: <ki-events@mit.edu>

Date: Friday, September 8, 2017 at 9:06 AM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Subject: Reminder – Register Today

 

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Pioneers of Cancer Cell Therapy:  Turbocharging the Immune System to Battle Cancer Cells — Success in Hematological Cancers vs. Solid Tumors

Curator: Aviva Lev-Ari, PhD, RN

Chimeric Antigen Receptor T-Cell Therapy: Players in Basic & Translational Research and Biotech/Pharma

The companies are teamed with academic pioneers:

  • Novartis with University of Pennsylvania;
  • Kite Pharma with the National Cancer Institute; 
  • Juno Therapeutics with Sloan Kettering,
  • the Fred Hutchinson Cancer Research Center in Seattle and Seattle Children’s Hospital.

cancer33

IMAGE SOURCE: National Cancer Institute

 

 “CAR-T cell immunotherapy” –  genetically modified T cells that are engineered to target specific tumor antigens and/or genes that are involved in survival, proliferation, and the enhancement of effector functions have been under intense research.

 

CAR technology was originally reported by Zelig Eshhar in 1993.

https://www.weizmann.ac.il/immunology/sci/EshharPage.html

Prof. Zelig Eshhar, Ph.D., served as Chairman of the Department of Immunology at the Weizmann Institute. Prof. Eshhar has been Chair of Scientific Advisory Board at TxCell S.A. since April 2016. Prof. Eshhar has been a Member of Scientific Advisory Board at Kite Pharma, Inc. since August 8, 2013. Prof. Eshhar served as a Member of Scientific Advisory Board at Intellect Neurosciences, Inc. since April 2006.

Prof. Eshhar pioneered the CAR approach (or T-Body as he termed it) to redirect T cells to recognize, engage and kill patient’s tumor cells by engineering them with a construct that combines the anti-target specificity of an antibody with T cell activation domains. Prof. Eshhar serves on several editorial boards, including Cancer Gene Therapy, Human Gene Therapy, Gene Therapy, Expert Opinion on Therapeutics, European Journal of Immunology and the Journal of Gene Medicine. He was a Research Fellow in the Department of Pathology at Harvard Medical School and in the Department of Chemical Immunology at the Weizmann Institute in Israel. His achievements were recognized by several international awards, most recently the CAR Pioneering award by the ATTACK European Consortium. Prof. Eshhar obtained his B.Sc. in Biochemistry and Microbiology and his M.Sc. in Biochemistry from the Hebrew University, and his Ph.D. in the Department of Immunology from the Weizmann Institute of Science.

http://www.bloomberg.com/research/stocks/people/person.asp?personId=32720993&privcapId=32390485

 

Zelig Eshhar and Carl H. June honored for research on T cell engineering for cancer immunotherapy

New Rochelle, NY, November 11, 2014–Zelig Eshhar, PhD, The Weizmann Institute of Science and Sourasky Medical Center, and Carl H. June, MD, PhD, Perelman School of Medicine, University of Pennsylvania, are co-recipients of the Pioneer Award, recognized for lentiviral gene therapy clinical trials and for their leadership and contributions in engineering T-cells capable of targeting tumors with antibody-like specificity through the development of chimeric antigen receptors (CARs). Human Gene Therapy, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers, is commemorating its 25th anniversary by bestowing this honor on the leading Pioneers in the field of cell and gene therapy selected by a blue ribbon panel* and publishing a Pioneer Perspective by the award recipients. The Perspectives by Dr. Eshhar and Dr. June are available free on the Human Gene Therapy website at http://www.liebertpub.com/hgt until December 11, 2014.

In his Pioneer Perspective entitled “From the Mouse Cage to Human Therapy: A Personal Perspective of the Emergence of T-bodies/Chimeric Antigen Receptor T Cells” Professor Eshhar chronicles his team’s groundbreaking contributions to the development of the CAR T-cell immunotherapeutic approach to treating cancer. He describes the method’s conceptual development including initial proof-of-concept, and the years of experimentation in mouse models of cancer. They first tested the CAR T-cells on tumors transplanted into mice then progressed to spontaneously developing cancers in immune-competent mice, which Dr. Eshhar describes as “a more suitable model that faithfully mimics cancer patients.” He recounts successful antitumor effects in mice with CAR modified T-cells injected directly into tumors, with effects seen at the injection site and at sites of metastasis, and even the potential of the CAR T-cells to prevent tumor development.

Dr. Carl H. June has led one of the clinical groups that has taken the CAR therapeutic strategy from the laboratory to the patients’ bedside, pioneering the use of CD19-specific CAR T-cells to treat patients with leukemia. In his Pioneer Perspective, “Toward Synthetic Biology with Engineered T Cells: A Long Journey Just Begun” Dr. June looks back on his long, multi-faceted career and describes how he combined his knowledge and research on immunology, cancer, and HIV to develop successful T-cell based immunotherapies. Among the lessons Dr. June has embraced throughout his career are to follow one’s passions. He also says that “accidents can be good: embrace the unexpected results and follow up on these as they are often times more scientifically interesting than predictable responses from less imaginative experiments.”

“These two extraordinary scientists made seminal contributions at key steps of the journey from bench to bedside for CAR T-cells,” says James M. Wilson, MD, PhD, Editor-in-Chief of Human Gene Therapy, and Director of the Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia.

SOURCE

http://www.eurekalert.org/pub_releases/2014-11/mali-ze111114.php

The General procedure of CAR-T cell therapy involves the follwoing steps:

1) Separate T cells from patient;

2) Engineer these T cells to express an artificial receptor, which is called “CAR” that usually targets tumor-specific antigen;

3) Expand the CAR T cells to a sufficient amount;

4) Re-introduce the CAR T cells to patient.

There are two major components that are critical to the CAR-T cell immunotherapy:

  • the design of CAR itself and
  • the choice of the targeted tumor specific antigen.

SOURCE

http://www.ochis.org/node/209

 

First publication on Adoptive transfer of genetically modified T cells is an attractive approach for generating antitumor immune responses

Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19

James N. Kochenderfer, Wyndham H. Wilson, John E. Janik, Mark E. Dudley, Maryalice Stetler-Stevenson, Steven A. Feldman, Irina Maric, Mark Raffeld, Debbie-Ann N. Nathan, Brock J. Lanier, Richard A. Morgan, Steven A. Rosenberg

Abstract

Adoptive transfer of genetically modified T cells is an attractive approach for generating antitumor immune responses. We treated a patient with advanced follicular lymphoma by administering a preparative chemotherapy regimen followed by autologous T cells genetically engineered to express a chimeric antigen receptor (CAR) that recognized the B-cell antigen CD19. The patient’s lymphoma underwent a dramatic regression, and B-cell precursors were selectively eliminated from the patient’s bone marrow after infusion of anti–CD19-CAR-transduced T cells. Blood B cells were absent for at least 39 weeks after anti–CD19-CAR-transduced T-cell infusion despite prompt recovery of other blood cell counts. Consistent with eradication of B-lineage cells, serum immunoglobulins decreased to very low levels after treatment. The prolonged and selective elimination of B-lineage cells could not be attributed to the chemotherapy that the patient received and indicated antigen-specific eradication of B-lineage cells. Adoptive transfer of anti–CD19-CAR-expressing T cells is a promising new approach for treating B-cell malignancies. This study is registered at www.clinicaltrials.gov as #NCT00924326.

SOURCE

According to Setting the Body’s ‘Serial Killers’ Loose on Cancer

After a long, intense pursuit, researchers are close to bringing to market a daring new treatment: cell therapy that turbocharges the immune system to fight cancer.

By ANDREW POLLACK  AUG. 1, 2016

http://www.nytimes.com/2016/08/02/health/cancer-cell-therapy-immune-system.html?_r=0

Dr. June’s 2011 publications did not cite Dr. Rosenberg’s paper [Blood, 2010] from the previous year, prompting Dr. Rosenberg to write a letter to The New England Journal of Medicine. Dr. June’s publications also did not acknowledge that the genetic construct he had used was the one he had obtained from Dr. Campana of St. Jude.

From the Lab to the bedside to the Out Patient Clinic

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New York Times Articles on Cancer Immunotherapy and Cancer Treatment Options

Curators: Aviva Lev-Ari, PhD, RN, Stephen J Williams, PhD and Tilda Barliya, PhD

The following articles, 

Here are some ways cancer can thwart the new immunotherapy drugs

Laurie McGinley July 13, 2016

https://www.washingtonpost.com/news/to-your-health/wp/2016/07/13/here-are-some-ways-cancer-can-thwart-the-new-immunotherapy-drugs/

and

The list of cancers that can be treated by immunotherapy keeps growing

By Laurie McGinley April 19

https://www.washingtonpost.com/news/to-your-health/wp/2016/04/19/breakthrough-cancer-therapy-shows-growing-promise/?tid=a_inl

were brought to my attention by Tilda Barliya, PhD, on our R&D Team, DrugDiscovery @LPBI Group, it stimulated the following curation in several Parts:

This article has three parts:

  • Part One: LPBI Group: A Key Opinion Leader (KOL) in Cancer and Genomics
  • Part Two: History of Cancer Immunotherapy
  • Part Three: New York Times Articles on Cancer Immunotherapy and Cancer Treatment Options

 

Part One:

LPBI Group: A Key Opinion Leader (KOL) in Cancer and Genomics

 

Immune System Stimulants: Articles of Note @pharmaceuticalintelligence.com

Immune-Oncology Molecules In Development & Articles on Topic in @pharmaceuticalintelligence.com

Curators: Stephen J Williams, PhD and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/01/11/articles-on-immune-oncology-molecules-in-development-pharmaceuticalintelligence-com/

Cancer Biology & Genomics for Disease Diagnosis, on Amazon since 8/11/2015

http://www.amazon.com/dp/B013RVYR2K

Genomics Orientations for Personalized Medicine, on Amazon since 11/23/2015

http://www.amazon.com/dp/B018DHBUO6

Genomics Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS & BioInformatics, Simulations and the Genome Ontology

https://pharmaceuticalintelligence.com/biomed-e-books/genomics-orientations-for-personalized-medicine/volume-two-genomics-methodologies-ngs-bioinformatics-simulations-and-the-genome-ontology/

Cancer Volume Two: Cancer Therapies: Metabolic, Genomics, Interventional, Immunotherapy and Nanotechnology in Therapy Delivery

https://pharmaceuticalintelligence.com/biomed-e-books/series-c-e-books-on-cancer-oncology/volume-2-immunotherapy-in-oncology/

Part Two:

History of Cancer Immunotherapy

Pioneers of Cancer Cell Therapy:  Turbocharging the Immune System to Battle Cancer Cells — Success in Hematological Cancers vs. Solid Tumors

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/08/19/pioneers-of-cancer-cell-therapy-turbocharging-the-immune-system-to-battle-cancer-cells-success-in-hematological-cancers-vs-solid-tumors/

In 1987, researchers identified cytotoxic T-lymphocyte antigen 4, or CTLA-4. Allison found that CTLA-4 prevents T cells from attacking tumor cells. He wondered whether blocking CTLA-4 would allow the immune system to make those attacks. In 1996, Allison showed that antibodies against CTLA-4 allowed the immune system to destroy tumors in mice.[2] In 1999, biotech firm Medarex acquired rights to the antibody. In 2010, Medarex acquirer Bristol-Myers Squibb reported that patients with metastatic melanoma lived an average of 10 months on the antibody, versus 6 months without it. It was the first time any treatment had extended life in advanced melanoma in a randomized trial.[2]

In the early 1990s, a biologist discovered a molecule expressed in dying T cells, which he called programmed death 1, or PD-1 and which he recognized as another disabler of T cells. An antibody that targeted PD-1 was developed and by 2008 produced remission in multiple subjects across multiple cancer types. In 2013, clinicians reported that across 300 patients tumors shrunk by about half or more in 31% of those with melanoma, 29% with kidney cancer and 17% with lung cancer.[2]

In 1997 rituximab, the first antibody treatment for cancer, was approved by the FDA for treatment of follicular lymphoma. Since this approval, 11 other antibodies have been approved for cancer; alemtuzumab (2001), ofatumumab (2009) and ipilimumab (2011).

In 2003 cytokines such as interleukin were administered.[3] The adverse effects of intravenously administered cytokines[4] led to the extraction, in vitro expansion against a tumour antigen and reinjection of the cells[5] with appropriate stimulatory cytokines.

However, with both anti–CTLA-4 and anti–PD-1, some tumors continued to grow before vanishing months later. Some patients kept responding after the antibody had been discontinued. Some patients, developed side effects including inflammation of the colon or of the pituitary gland.[2]

The first cell-based immunotherapy cancer vaccine, sipuleucel-T, was approved in 2010 for the treatment of prostate cancer.[6][7]

After success harvesting T cells from tumors, expanding them in the lab and reinfusing them into patients reduced tumors, in 2010, Steven Rosenberg announced chimeric antigen receptor therapy, or CAR therapy. This technique is a personalized treatment that involves genetically modifying each patient’s T cells to target tumor cells. It produced complete remission in a majority of leukemia patients, although some later relapsed.[2]

By mid 2016 the FDA had approved one PD-L1 inhibitor (atezolizumab) and two PD-1 inhibitors (nivolumab and pembrolizumab).

SOURCE

https://en.wikipedia.org/wiki/Cancer_immunotherapy

Part Three:

New York Times Articles on Cancer Immunotherapy and Cancer Treatment Options

 

  1. What Is Immunotherapy? The Basics on These Cancer Treatments

    Some of the most promising advances in cancer research in recent years involve treatments known as immunotherapy. These advances are spurring billions of dollars in investment by drug companies, and are leading to hundreds of

  2. Immunotherapy Offers Hope to a Cancer Patient, but No Certainty

    declared him in remission. It was a result that put him at the vanguard of a new generation of cancer treatment called immunotherapy that casts into sharp relief the harshness of how we have long treated cancer and the less grueling

  3. Have You Received Immunotherapy Treatment for Cancer?

    The New York Times would like to hear from doctors and patients who have experience giving or receiving immunotherapy treatment for cancer.

  4. Immunotherapy Drug Fails Lung Cancer Trial

    The hot new field of immunotherapy got a shock on Friday when a best-selling new drug failed as an initial treatment for lung cancer in a clinical trial. Bristol-Myers Squibb said Friday that the drug, Opdivo, had not slowed the

  5. F.D.A. Approves Immunotherapy Drug for Treatment of Bladder Cancer

    The Food and Drug Administration on Wednesday approved a newimmunotherapy drug from Roche to treat bladder cancer, a form of cancer for which there have been no significant new medicines in years. The drug, called Tecentriq, is the

  6. Sean Parker, a Facebook and Napster Pioneer, to Start CancerImmunotherapy Effort

    media as the early president of Facebook. Now he wants to pioneer in a field that is already jumping with activity: cancer immunotherapy. Mr. Parker is announcing Wednesday that he is donating $250 million to a new effort that will

  7. Harnessing the Immune System to Fight Cancer

    Sloan Kettering Cancer Center in New York, recommended an experimental treatment: immunotherapy. Rather than attacking the cancer directly, as chemo does, immunotherapy tries to rally the patient’s own immune

  8. Cancer-Drug Ads vs. Cancer-Drug Reality

    She also took part in a clinical trial at Johns Hopkins for Opdivo, an immunotherapy drug made by the pharmaceutical company Bristol-Myers Squibb. Briefly stated, immunotherapy is a recently developed, highly

  9. Sean Parker on Cancer Research

    Sean Parker discusses his support of immunotherapy research.

  10. Paid Notice: Deaths SPRAYREGEN, NICHOLAS (NICK)

    family and many friends. Contributions in his memory may be made to Memorial Sloan Kettering Cancer Center, Melanoma and Immunotherapy Research under Dr. Jedd Wolchok. 1/3

    11. Paid Notice: Deaths SPRAYREGEN, NICHOLAS (NICK)

    St. and Amsterdam Ave. Contributions in his memory may be made to Memorial Sloan Kettering Cancer Center, Melanoma and Immunotherapy Research under Dr. Jedd Wolchok. 1/3

    12. Setting the Body’s ‘Serial Killers’ Loose on Cancer

    Sloan Kettering Cancer Center. This radical, science-fictionlike therapy differs sharply from the more established type of immunotherapy, developed by other researchers. Those off-the-shelf drugs, known as checkpoint inhibitors,

SOURCE

http://query.nytimes.com/search/sitesearch/?action=click&contentCollection&region=TopBar&WT.nav=searchWidget&module=SearchSubmit&pgtype=Homepage#/immunotherapy/since1851/allresults/2/

 Additional Readings:

More women with cancer in one breast are having double mastectomies

Medicare considers overhaul of doctors’ payments for cancer drugs

Paul Allen announces $100 million gift to expand “frontiers of bioscience”

Life sciences a priority for Sean Parker’s new $600 million foundation

Cornell study finds some people may be genetically programmed to be vegetarians

Mom’s and — surprise! — dad’s pre-pregnancy caffeine intake may affect miscarriage risk, NIH study warns

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CHI’s NK Cell-Based Cancer Immunotherapy Symposium, September 19 in Boston

Reporter: Aviva Lev-Ari, PhD, RN

 

Announcement from LPBI Group: key code LPBI16 for Exclusive Discount to attend Boston’s Discovery on Target (September 2016)

https://pharmaceuticalintelligence.com/2016/05/13/announcement-from-lpbi-group-key-code-lpbi16-for-exclusive-discount-to-attend-bostons-discovery-on-target-september-2016/

DOT-150x150

DOT-NCT-700x150

FEATURED SESSION:

Natural killer (NK) cells have been known to have advantages over T cells, yet their therapeutic potential in the clinic has been largely unexplored.

Cambridge Healthtech Institute’s NK Cell-Based Cancer Immunotherapy Symposium, September 19 in Boston, is dedicated to the exploration of utilizing NK cells for new adoptive cell therapies, including updates from ongoing clinical studies.

NK CELL IMMUNO-ONCOLOGY AND CLINICAL STUDIES

Harnessing Adaptive NK Cells in Cancer Therapy

Karl-Johan Malmberg, M.D., Ph.D., Professor, Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital

  • We have recently completed a Phase I/II clinical trial with transfer of haploidentical NK cells to patients with high-risk myelodysplastic syndrome. Six of the 16 treated patients achieved morphological complete remission and five of these underwent allogeneic stem cell transplantation resulting in long-term survival in four patients. The quality and number of infused NK cells as well as their transient engraftment in the recipient correlated with decrease in mutational burden and clinical outcomes. These results suggest that adoptive transfer of allogeneic NK cells may hold utility as a bridge to transplant in patients who are refractory to induction therapy. Current efforts to selectively expand metabolically optimized adaptive NK cells for the next generation NK cell cancer immunotherapy will be discussed.

Update on Systemic and Locoregional Cancer Immunotherapy with IL-21-Expanded NK Cells

Dean Anthony Lee, M.D., Ph.D., Professor, Pediatrics; Director, Cellular Therapy and Cancer Immunotherapy Program, Nationwide Children’s Hospital; James Comprehensive Cancer Center/Solove Research Institute, The Ohio State University

  • The ability to generate clinical-grade NK cell products of sufficient purity, number, and function has enabled broader application of adoptive NK cell therapy in clinical trials. We translated our IL-21-based NK cell expansion platform to clinical grade and scale and initiated 7 clinical trials that administer NK cell immunotherapy with high cell doses or repeated dosing in transplant, adjuvant, or stand-alone settings. These trials have collectively delivered approximately 150 infusions to over 60 patients at doses of up to 10e8/kg. We will discuss the importance of STAT3 signaling in this setting, describe early outcome and correlative data from these studies, and present preclinical data supporting future clinical trials that build on this platform.

REGISTER

BY AUGUST 12 TO

SAVE UP TO $200

VISIT

WEBSITE

DOWNLOAD PDF AGENDA

Suggested Event Package

SYMPOSIUM

NK Cell-Based Cancer Immunotherapy

SEPT. 19

CONFERENCE

Antibodies Against Membrane Protein Targets (Part One)

SEPT. 20-21

CONFERENCE

Antibodies Against Membrane Protein Targets (Part Two)

SEPT. 21-22

The exhibit hall was sold out in 2015, so please contact us early to reserve your place. To customize your sponsorship or exhibit package for 2016, contact:

Jon Stroup

Sr. Business Development Manager

P: 781-972-5483

E: jstroup@healthtech.com

Sponsorship/Exhibitor Information >>

 

DiscoveryOnTarget.com | Register by August 12 to SAVE up to $200 | Download PDF Agenda

Cambridge Healthtech Institute | 250 First Avenue, Suite 300, Needham, MA 02494 | www.healthtech.com | 781-972-5400

SOURCE

From: NK Cell Symposium <heidio@healthtech.com>

Date: Tuesday, August 9, 2016 at 1:40 PM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Subject: NK Cells for Adoptive Therapies: The Future of Cancer Immunotherapy?

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