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2022 FDA Drug Approval List, 2022 Biological Approvals and Approved Cellular and Gene Therapy Products

Posted in cell-based therapy, Drug Discovery Chemistry, FDA, FDA, CE Mark & Global Regulatory Affairs: process management and strategic planning - GCP, GLP, ISO 14155, Pharmaceutical Discovery, Pharmaceutical Drug Discovery, Pharmaceutical R&D Informatics, Pharmacodynamics and Pharmacokinetics, Regenerative Biology and Medicine on January 17, 2023| Leave a Comment »

2022 FDA Drug Approval List, 2022 Biological Approvals and Approved Cellular and Gene Therapy Products

 

 

Reporter: Aviva Lev-Ari, PhD, RN

SOURCE

Tal Bahar’s post on LinkedIn on 1/17/2023

Novel Drug Approvals for 2022

FDA’s Center for Drug Evaluation and Research (CDER)

New Molecular Entities (“NMEs”)

  • Some of these products have never been used in clinical practice. Below is a listing of new molecular entities and new therapeutic biological products that CDER approved in 2022. This listing does not contain vaccines, allergenic products, blood and blood products, plasma derivatives, cellular and gene therapy products, or other products that the Center for Biologics Evaluation and Research approved in 2022. 
  • Others are the same as, or related to, previously approved products, and they will compete with those products in the marketplace. See Drugs@FDA for information about all of CDER’s approved drugs and biological products. 

Certain drugs are classified as new molecular entities (“NMEs”) for purposes of FDA review. Many of these products contain active moieties that FDA had not previously approved, either as a single ingredient drug or as part of a combination product. These products frequently provide important new therapies for patients. Some drugs are characterized as NMEs for administrative purposes, but nonetheless contain active moieties that are closely related to active moieties in products that FDA has previously approved. FDA’s classification of a drug as an “NME” for review purposes is distinct from FDA’s determination of whether a drug product is a “new chemical entity” or “NCE” within the meaning of the Federal Food, Drug, and Cosmetic Act. 

INNOVATION   PREDICTABILITY   ACCESS FDA’s Center for Drug Evaluation and Research

January 2023

Table of Contents

 SOURCE

2022 Biological Approvals

The Center for Biologics Evaluation and Research (CBER) regulates products under a variety of regulatory authorities.  See the Development & Approval Process page for a description of what products are approved as Biologics License Applications (BLAs), Premarket Approvals (PMAs), New Drug Applications (NDAs) or 510Ks.

Biologics License Applications and Supplements

New BLAs (except those for blood banking), and BLA supplements that are expected to significantly enhance the public health (e.g., for new/expanded indications, new routes of administration, new dosage formulations and improved safety).

Other Applications Approved or Cleared by the Center for Biologics Evaluation and Research (CBER)

Medical devices involved in the collection, processing, testing, manufacture and administration of licensed blood, blood components and cellular products.

Key Resources

SOURCE

https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/2022-biological-approvals

 

Approved Cellular and Gene Therapy Products

Below is a list of licensed products from the Office of Tissues and Advanced Therapies (OTAT).

Approved Products

 

Resources For You

SOURCE

https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/approved-cellular-and-gene-therapy-products

 

2022 forecast: Cell, gene therapy makers push past regulatory, payer hurdles to set up high hopes for next year

By Arlene Weintraub
Dec 22, 2021 03:00am

There are five FDA-approved CAR-T treatments for blood cancers and two gene therapies to treat rare diseases now on the market in the U.S. The late-stage pipeline could produce several more cancer CAR-Ts and gene therapies to treat a range of diseases.

RELATED: ASH: Bristol Myers’ Breyanzi, Gilead’s Yescarta lock horns in race to move CAR-T therapy to earlier lymphoma

One of the biggest races to watch in the cell therapy space will be that between Gilead Sciences’ Yescarta and Bristol Myers Squibb’s Breyanzi, both of which are gunning to move their CAR-Ts into earlier lines of treatment in large B-cell lymphoma (LBCL). At ASH, both companies rolled out impressive data from their trials in the second-line setting, but Gilead could have the upper hand by virtue of its three-year head start in the market, analysts said. Gilead expects to hear from the FDA on a label expansion in the second-line setting in April.

SOURCE

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New avenues for research in membrane biology reveals the mobility of protein at work

Posted in Cell Biology, cell-based therapy, Medical Devices R&D and Inventions, Medical Imaging Technology, Proteins, tagged , , , , , , , , , on August 23, 2021| Leave a Comment »

New avenues for research in membrane biology reveals the mobility of protein at work

Curator and Reporter: Dr. Premalata Pati, Ph.D., Postdoc

Membrane proteins (MPs) are proteins that exist in the plasma membrane and conduct a variety of biological functions such as ion transport, substrate transport, and signal transduction. MPs undergo function-related conformational changes on time intervals spanning from nanoseconds to seconds. Many MP structures have been solved thanks to recent developments in structural biology, particularly in single-particle cryo-Electron Microscopy (cryo-EM). Obtaining time-resolved dynamic information on MPs in their membrane surroundings, on the other hand, remains a significant difficulty.

OmpG (Open state) in a fully hydrated dimyristoylphosphatidylcholine (DMPC) bilayer. The protein is shown in light green cartoon. Lipids units are depicted in yellow, while their phosphate and choline groups are illustrated as orange and green van der Waals spheres, respectively. Potassium and chloride counterions are shown in green and purple, respectively. A continuous and semi-transparent cyan representation is used for water.
https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-021-24660-1/MediaObjects/41467_2021_24660_MOESM1_ESM.pdf

Weill Cornell Medicine (WCM) researchers have found that they can record high-speed protein movements while linking them to function. The accomplishment should allow scientists to examine proteins in more depth than ever before, and in theory, it should allow for the development of drugs that work better by hitting their protein targets much more effectively.

The researchers utilized High-Speed Atomic Force Microscopy (HS-AFM) to record the rapid motions of a channel protein and published in a report in Nature Communications on July 16. Such proteins generally create channel or tube-like structures in cell membranes, which open to allow molecules to flow under particular conditions. The researchers were able to record the channel protein’s rapid openings and closings with the same temporal resolution as single channel recordings, a typical technique for recording the intermittent passage of charged molecules through the channel.

Senior author Simon Scheuring, professor of physiology and biophysics in anesthesiology at WCM, said,

There has been a significant need for a tool like this that achieves such a high bandwidth that it can ‘see’ the structural variations of molecules as they work.

Researchers can now produce incredibly detailed photographs of molecules using techniques like X-ray crystallography and electron microscopy, showing their structures down to the atomic scale. The average or dominant structural positionings, or conformations, of the molecules, are depicted in these “images,” which are often calculated from thousands of individual photos. In that way, they’re similar to the long-exposure still photos from the dawn of photography.

Many molecules, on the other hand, are flexible and always-moving machinery rather than fixed structures. Scientists need to generate videos, not still photos, to reveal how such molecules move as they work, to see how their motion translates to function to catch their critical functional conformations, which may only exist for a brief moment. Current techniques for dynamic structural imaging, on the other hand, have several drawbacks, one of which being the requirement for fluorescent tags to be inserted on the molecules being photographed in many cases.

Scheuring and his lab were early adopters of the tag-free HS-AFM approach for studying molecular dynamics. The technology, which can photograph molecules in a liquid solution similar to a genuine cellular environment, employs an extremely sensitive probe, similar to a record player’s stylus, to feel its way over a molecule and therefore build up a picture of its structure. Standard HS-AFM isn’t quick enough to capture the high-speed dynamics of many proteins, but Scheuring and colleagues have developed a modified version, HS-AFM height spectroscopy (HS-AFM-HS), that works much faster by collecting dynamic changes in only one dimension: height.

The researchers used HS-AFM-HS to record the opening and closing of a relatively simple channel protein, OmpG, found in bacteria and widely studied as a model channel protein in the new study, led by the first author Raghavendar Reddy Sanganna Gari, a postdoctoral research associate in Scheuring’s laboratory. They were able to monitor OmpG gating at an effective rate of roughly 20,000 data points per second, seeing how it transitioned from open to closed states or vice versa as the acidity of the surrounding fluid varied.

More significantly, they were able to correlate structural dynamics with functional dynamics in a membrane protein of this size for the first time in a partnership with Crina Nimigean, professor of physiology and biophysics in anesthesiology, and her group at WCM.

The demonstration opens the door for a wider application of this method in basic biology and drug development.

Sanganna Gari stated,

We’re now in an exciting period of HS-AFM technology, for example using this technique to study how some drugs modulate the structural dynamics of the channel proteins they target.

Main Source

Technique reveals proteins moving as they work. By Jim Schnabel in Cornell Chronicle, August 16, 2021.

https://news.cornell.edu/stories/2021/08/technique-reveals-proteins-moving-they-work

Other Related Articles published in this Open Access Online Scientific Journal include the following:

Cryo-EM disclosed how the D614G mutation changes SARS-CoV-2 spike protein structure.

Reporter: Dr. Premalata Pati, Ph.D., Postdoc

https://pharmaceuticalintelligence.com/2021/04/10/cryo-em-disclosed-how-the-d614g-mutation-changes-sars-cov-2-spike-protein-structure/

Proteins, Imaging and Therapeutics

Larry H Bernstein, MD, FCAP, Curator, LPBI

https://pharmaceuticalintelligence.com/2015/10/01/proteins-imaging-and-therapeutics/

From High-Throughput Assay to Systems Biology: New Tools for Drug Discovery

Curator: Stephen J. Williams, PhD

https://pharmaceuticalintelligence.com/2021/07/19/from-high-throughput-assay-to-systems-biology-new-tools-for-drug-discovery/

Imaging break-through: Fusion of microscopy and mass spectrometry produces detailed map of protein distribution

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2015/03/18/imaging-break-through-fusion-of-microscopy-and-mass-spectrometry-produces-detailed-map-of-protein-distribution/

Advanced Microscopic Imaging

Larry H Bernstein, MD, FCAP, Curator, LPBI

https://pharmaceuticalintelligence.com/2016/02/07/advanced-microscopic-imaging/

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Human personalized autologous cell therapy for Parkinson’s Disease

Posted in Autologous Cell Therapy, Biological Engineering, Biological Networks, Biomarkers & Medical Diagnostics, Biotechnology, Cell Biology, Cell Biology, Signaling & Cell Circuits, Cell Processing System in Cell Therapy Process Development, cell-based therapy, Cerebrovascular and Neurodegenerative Diseases, Competition in regenerative stem cell science, Genomic Endocrinology, hNPCs, Innovations in Neurophysiology & Neuropsychology, Neurodegenerative Diseases, Neurohumoral Transmission, Neurological Diseases, Neuronal Circuits, Neuroscience, Parkinson's disease dyskinesia levodopa, Patient-centered Medicine, Personal Health Applications: Tech Innovations serves HealhCare, Personalized and Precision Medicine & Genomic Research, Signaling & Cell Circuits, stem cell biology and patient-specific, Stem Cells for Regenerative Medicine, tagged , , , , on December 2, 2019| Leave a Comment »

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Parkinson’s Disease (PD), characterized by both motor and non-motor system pathology, is a common neurodegenerative disorder affecting about 1% of the population over age 60. Its prevalence presents an increasing social burden as the population ages. Since its introduction in the 1960’s, dopamine (DA)-replacement therapy (e.g., L-DOPA) has remained the gold standard treatment. While improving PD patients’ quality of life, the effects of treatment fade with disease progression and prolonged usage of these medications often (>80%) results in side effects including dyskinesias and motor fluctuations. Since the selective degeneration of A9 mDA neurons (mDANs) in the substantia nigra (SN) is a key pathological feature of the disease and is directly associated with the cardinal motor symptoms, dopaminergic cell transplantation has been proposed as a therapeutic strategy.

 

Researchers showed that mammalian fibroblasts can be converted into embryonic stem cell (ESC)-like induced pluripotent stem cells (iPSCs) by introducing four transcription factors i.e., Oct4, Sox2, Klf4, and c-Myc. This was then accomplished with human somatic cells, reprogramming them into human iPSCs (hiPSCs), offering the possibility of generating patient-specific stem cells. There are several major barriers to implementation of hiPSC-based cell therapy for PD. First, probably due to the limited understanding of the reprogramming process, wide variability exists between the differentiation potential of individual hiPSC lines. Second, the safety of hiPSC-based cell therapy has yet to be fully established. In particular, since any hiPSCs that remain undifferentiated or bear sub-clonal tumorigenic mutations have neoplastic potential, it is critical to eliminate completely such cells from a therapeutic product.

 

In the present study the researchers established human induced pluripotent stem cell (hiPSC)-based autologous cell therapy. Researchers reported a platform of core techniques for the production of mDA progenitors as a safe and effective therapeutic product. First, by combining metabolism-regulating microRNAs with reprogramming factors, a method was developed to more efficiently generate clinical grade iPSCs, as evidenced by genomic integrity and unbiased pluripotent potential. Second, a “spotting”-based in vitro differentiation methodology was established to generate functional and healthy mDA cells in a scalable manner. Third, a chemical method was developed that safely eliminates undifferentiated cells from the final product. Dopaminergic cells thus produced can express high levels of characteristic mDA markers, produce and secrete dopamine, and exhibit electrophysiological features typical of mDA cells. Transplantation of these cells into rodent models of PD robustly restored motor dysfunction and reinnervated host brain, while showing no evidence of tumor formation or redistribution of the implanted cells.

 

Together these results supported the promise of these techniques to provide clinically applicable personalized autologous cell therapy for PD. It was recognized by researchers that this methodology is likely to be more costly in dollars and manpower than techniques using off-the-shelf methods and allogenic cell lines. Nevertheless, the cost for autologous cell therapy may be expected to decrease steadily with technological refinement and automation. Given the significant advantages inherent in a cell source free of ethical concerns and with the potential to obviate the need for immunosuppression, with its attendant costs and dangers, it was proposed that this platform is suitable for the successful implementation of human personalized autologous cell therapy for PD.

 

References:

 

https://www.jci.org/articles/view/130767/pdf?elqTrackId=2fd7d0edee744f9cb6d70a686d7b273b

 

https://www.ncbi.nlm.nih.gov/pubmed/31714896

 

https://www.ncbi.nlm.nih.gov/pubmed/23666606

 

https://www.ncbi.nlm.nih.gov/pubmed/27343168

 

https://www.ncbi.nlm.nih.gov/pubmed/21495962

 

https://www.ncbi.nlm.nih.gov/pubmed/28083784

 

https://www.ncbi.nlm.nih.gov/pubmed/20336395

 

https://www.ncbi.nlm.nih.gov/pubmed/28585381

 

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Extracellular RNA and their carriers in disease diagnosis and therapy

Posted in Advanced Drug Manufacturing Technology, Bioengineering & reverse engineering design, BioIT: BioInformatics, NGS, Clinical & Translational, Pharmaceutical R&D Informatics, Clinical Genomics, Cancer Informatics, Biological Engineering, Biological Networks, Biological Networks, Gene Regulation and Evolution, Biomarkers & Medical Diagnostics, Biotechnology, Cancer and Current Therapeutics, cell-based therapy, Chemical Genetics, Clinical Diagnostics, Clinical Genomics, Disease Biology, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Exosomes: Natural Carriers for siRNA Delivery, Gene Therapy & Gene Editing Development, Genetics & Innovations in Treatment, Genomic Testing: Methodology for Diagnosis, Microvesicle, mRNA, mRNA platform in Drug DIscovery, mRNA Therapeutics, Population genetics, Population Health Management, Population Health Management, Genetics & Pharmaceutical, RNA Biology, RNA Biology, Cancer and Therapeutics, RNA interference (RNAi) therapeutic, Transformative Technologies in Healthcare, tagged , , , , on May 4, 2019| Leave a Comment »

Extracellular RNA and their carriers in disease diagnosis and therapy, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 1: Next Generation Sequencing (NGS)

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

RNA plays various roles in determining how the information in our genes drives cell behavior. One of its roles is to carry information encoded by our genes from the cell nucleus to the rest of the cell where it can be acted on by other cell components. Rresearchers have now defined how RNA also participates in transmitting information outside cells, known as extracellular RNA or exRNA. This new role of RNA in cell-to-cell communication has led to new discoveries of potential disease biomarkers and therapeutic targets. Cells using RNA to talk to each other is a significant shift in the general thought process about RNA biology.

 

Researchers explored basic exRNA biology, including how exRNA molecules and their transport packages (or carriers) were made, how they were expelled by producer cells and taken up by target cells, and what the exRNA molecules did when they got to their destination. They encountered surprising complexity both in the types of carriers that transport exRNA molecules between cells and in the different types of exRNA molecules associated with the carriers. The researchers had to be exceptionally creative in developing molecular and data-centric tools to begin making sense of the complexity, and found that the type of carrier affected how exRNA messages were sent and received.

 

As couriers of information between cells, exRNA molecules and their carriers give researchers an opportunity to intercept exRNA messages to see if they are associated with disease. If scientists could change or engineer designer exRNA messages, it may be a new way to treat disease. The researchers identified potential exRNA biomarkers for nearly 30 diseases including cardiovascular disease, diseases of the brain and central nervous system, pregnancy complications, glaucoma, diabetes, autoimmune diseases and multiple types of cancer.

 

As for example some researchers found that exRNA in urine showed promise as a biomarker of muscular dystrophy where current studies rely on markers obtained through painful muscle biopsies. Some other researchers laid the groundwork for exRNA as therapeutics with preliminary studies demonstrating how researchers might load exRNA molecules into suitable carriers and target carriers to intended recipient cells, and determining whether engineered carriers could have adverse side effects. Scientists engineered carriers with designer RNA messages to target lab-grown breast cancer cells displaying a certain protein on their surface. In an animal model of breast cancer with the cell surface protein, the researchers showed a reduction in tumor growth after engineered carriers deposited their RNA cargo.

 

Other than the above research work the scientists also created a catalog of exRNA molecules found in human biofluids like plasma, saliva and urine. They analyzed over 50,000 samples from over 2000 donors, generating exRNA profiles for 13 biofluids. This included over 1000 exRNA profiles from healthy volunteers. The researchers found that exRNA profiles varied greatly among healthy individuals depending on characteristics like age and environmental factors like exercise. This means that exRNA profiles can give important and detailed information about health and disease, but careful comparisons need to be made with exRNA data generated from people with similar characteristics.

 

Next the researchers will develop tools to efficiently and reproducibly isolate, identify and analyze different carrier types and their exRNA cargos and allow analysis of one carrier and its cargo at a time. These tools will be shared with the research community to fill gaps in knowledge generated till now and to continue to move this field forward.

 

References:

 

https://www.nih.gov/news-events/news-releases/scientists-explore-new-roles-rna

 

https://www.cell.com/consortium/exRNA

 

https://www.sciencedaily.com/releases/2016/06/160606120230.htm

 

https://www.pasteur.fr/en/multiple-roles-rnas

 

https://www.nature.com/scitable/topicpage/rna-functions-352

 

https://www.umassmed.edu/rti/biology/role-of-rna-in-biology/

 

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Mitochondria Replacement Therapy

Posted in Cell Biology, Cell Biology, Signaling & Cell Circuits, cell-based therapy, Developmental biology, Embryology, Gene Therapy & Gene Editing Development, Preimplantation Genetic Diagnosis and Reproductive Genomics, Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics, Reproductive Biology & Bio Instrumentation, Signaling & Cell Circuits, Single Cell Genomics, stem cell biology and patient-specific, tagged , , , , on April 14, 2019| Leave a Comment »

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Leigh syndrome is one of the hundreds of so-called mitochondrial diseases, which are caused by defects in the mitochondria that produce 90 percent of the body’s energy. These disorders are rare; about 1,000 to 4,000 babies in the United States are born with one every year. But they are devastating and can result in grave impairment of nearly any bodily system. They are largely untreatable, uniformly incurable and very difficult to screen.

 

Leigh syndrome is a terrible disease. It emerges shortly after birth and claims one major organ after another. Movement becomes difficult, and then impossible. A tracheotomy and feeding tube are often necessary by toddlerhood, and as the disease progresses, lungs frequently have to be suctioned manually. Most children with the condition die by the age of 5 or 6.

 

Scientists have devised a procedure called mitochondrial replacement therapy (M.R.T.) that involves transplanting the nucleus of an affected egg (mitochondrial diseases are passed down from the mother’s side) into an unaffected one whose nucleus has been removed. The procedure is sometimes called “three-parent in vitro fertilization”. Mitochondria contain a minuscule amount of DNA, any resulting embryo would have mitochondrial DNA from the donor egg and nuclear DNA from each of its parents.

 

After decades of careful study in cell and animal research M.R.T. is now finally being tested in human clinical trials by doctors in Britain (no births confirmed yet officially). In the United States, however, this procedure is effectively illegal. M.R.T. does not involve altering any genetic code. Defective mitochondria are swapped out for healthy ones.

 

Mitochondrial DNA governs only a handful of basic cellular functions. It is separate from nuclear DNA, which helps determine individual traits like physical appearance, intelligence and personality. That means M.R.T. cannot be used to produce the genetically enhanced “designer babies” and thus should be allowed in humans. But, there is no way to know how safe or effective M.R.T. is until doctors and scientists test it in humans.

 

References:

 

 

https://pharmaceuticalintelligence.com/2016/10/07/the-three-parent-technique-to-avoid-mitochondrial-disease-in-embryo/

 

 

 

 

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Immunoediting can be a constant defense in the cancer landscape

Posted in Anticancer Resistance, Apoptosis, BioIT: BioInformatics, NGS, Clinical & Translational, Pharmaceutical R&D Informatics, Clinical Genomics, Cancer Informatics, Breast Cancer - impalpable breast lesions, Cancer - General, Cancer and Current Therapeutics, CANCER BIOLOGY & Innovations in Cancer Therapy, Cancer Genomics, Cancer Informatics, cancer metabolism, Cancer Prevention: Research & Programs, Cancer Screening, Cancer Surgery of the Heart, Cancer Vaccines: Targeting Cancer Genes for Immunotherapy, Cancer-Immune Interactions, Cell Biology, Cell Biology, Signaling & Cell Circuits, Cell death pathways, Cell Processing System in Cell Therapy Process Development, cell-based therapy, Childhood cancer, Circulating Tumor Cells (CTC), combination immunotherapies., Efficacy of Anti-Tumor T Cells, Engineering Better T Cells, Engineering Enhanced Cancer Vaccines, Funding Opportunities for Cancer Research, Human Immune System in Health and in Disease, Imaging-based Cancer Patient Management, Immune Modulatory, Immuno-Oncology & Genomics, Immunology, Immunotherapy, Infectious Disease Immunodiagnostics, Innovation in Immunology Diagnostics, Integrin-targeted Combination Immunotherapy, Liquid Biopsy Chip detects an array of metastatic cancer cell markers in blood, Liquid Biopsy: Circulating Tumor Cells in Urine and Blood, Metabolic Immuno-Oncology, Microbiome and Responses to Cancer Therapy, MicroEngineering Cell-Tissue & Systems, Modulating Macrophages in Cancer Immunotherapy, Monoclonal Immunotherapy, NK Cell-Based Cancer Immunotherapy, Pancreatic cancer, Pharmacotherapy and Cell Activity, Population Health Management, Population Health Management, Genetics & Pharmaceutical, Population Health Management, Nutrition and Phytochemistry, Precision Cancer Medicine, Prostate Cancer: Monitoring vs Treatment, RNA Biology, Cancer and Therapeutics, Signaling & Cell Circuits, Single Cell Genomics, stem cell biology and patient-specific, Stem Cells for Regenerative Medicine, Synergistic Innate and Adaptive Immunotherapy, Synthetic Immunology: Hacking Immune Cells, Universal Immune Cell Therapies (uICT), Voices of Patients and Healthcare Providers, tagged , , , , on March 16, 2019| Leave a Comment »

Immuno-editing can be a constant defense in the cancer landscape, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 1: Next Generation Sequencing (NGS)

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

There are many considerations in the cancer immunoediting landscape of defense and regulation in the cancer hallmark biology. The cancer hallmark biology in concert with key controls of the HLA compatibility affinity mechanisms are pivotal in architecting a unique patient-centric therapeutic application. Selection of random immune products including neoantigens, antigens, antibodies and other vital immune elements creates a high level of uncertainty and risk of undesirable immune reactions. Immunoediting is a constant process. The human innate and adaptive forces can either trigger favorable or unfavorable immunoediting features. Cancer is a multi-disease entity. There are multi-factorial initiators in a certain disease process. Namely, environmental exposures, viral and / or microbiome exposure disequilibrium, direct harm to DNA, poor immune adaptability, inherent risk and an individual’s own vibration rhythm in life.

 

When a human single cell is crippled (Deranged DNA) with mixed up molecular behavior that is the initiator of the problem. A once normal cell now transitioned into full threatening molecular time bomb. In the modeling and creation of a tumor it all begins with the singular molecular crisis and crippling of a normal human cell. At this point it is either chop suey (mixed bit responses) or a productive defensive and regulation response and posture of the immune system. Mixed bits of normal DNA, cancer-laden DNA, circulating tumor DNA, circulating normal cells, circulating tumor cells, circulating immune defense cells, circulating immune inflammatory cells forming a moiety of normal and a moiety of mess. The challenge is to scavenge the mess and amplify the normal.

 

Immunoediting is a primary push-button feature that is definitely required to be hit when it comes to initiating immune defenses against cancer and an adaptation in favor of regression. As mentioned before that the tumor microenvironment is a “mixed bit” moiety, which includes elements of the immune system that can defend against circulating cancer cells and tumor growth. Personalized (Precision-Based) cancer vaccines must become the primary form of treatment in this case. Current treatment regimens in conventional therapy destroy immune defenses and regulation and create more serious complications observed in tumor progression, metastasis and survival. Commonly resistance to chemotherapeutic agents is observed. These personalized treatments will be developed in concert with cancer hallmark analytics and immunocentrics affinity and selection mapping. This mapping will demonstrate molecular pathway interface and HLA compatibility and adaptation with patientcentricity.

References:

 

https://www.linkedin.com/pulse/immunoediting-cancer-landscape-john-catanzaro/

 

https://www.cell.com/cell/fulltext/S0092-8674(16)31609-9

 

https://www.researchgate.net/publication/309432057_Circulating_tumor_cell_clusters_What_we_know_and_what_we_expect_Review

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190561/

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840207/

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593672/

 

https://www.frontiersin.org/articles/10.3389/fimmu.2018.00414/full

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593672/

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190561/

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4388310/

 

https://www.linkedin.com/pulse/cancer-hallmark-analytics-omics-data-pathway-studio-review-catanzaro/

 

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Gene-editing Second International Summit in Hong Kong: George Church, “Let’s be quantitative before we start being accusatory”

Posted in cell-based therapy, CRISPR applied to Human Germ Line, Personalized and Precision Medicine & Genomic Research on November 29, 2018| Leave a Comment »

Gene-editing Second International Summit in Hong Kong: George Church, “Let’s be quantitative before we start being accusatory”

Reporter: Aviva Lev-Ari, PhD, RN

2.1.4.3

2.1.4.3   Gene-editing Second International Summit in Hong Kong: George Church, “Let’s be quantitative before we start being accusatory”, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 2: CRISPR for Gene Editing and DNA Repair

UPDATED on 11/30/2018

Gene editing takes a foreboding leap forward

He Jiankui. Photo: Zhang Wei/Chinese News Service/VCG via Getty Images

 

China is temporarily suspending the work of scientists who claimed twins were born after being genetically edited as embryos.

Why it matters: The scientific consensus is that gene editing embryos at this stage of science is “irresponsible.” But, while this particular experiment has not been verified, the fact is the technology is available to researchers, so there’s a growing call for international limitations on its use.

ICYMI: Chinese scientist He Jiankui announced earlier this week that twins were born after he used the gene-editing tool CRISPR-Cas9 to cut the CCR5 gene that’s known to play a role in HIV infection.

  • He stirred even more dismay when he mentioned the possibility of a second pregnancy.
  • China currently bans human implantation of gene-edited embryos. Its Ministry of Science and Technology is investigating the claims, per Xinhua.

There are concerns about the safety, efficacy and possible mosaicism, where a person can contain genes in both its edited and unedited forms, from cutting genes.

  • Editing embryos raises an even bigger concern: The genetic changes and all the unknowns around them can be passed down to future generations.

Between the lines: Not everyone viewed it as a complete disaster. For instance, Harvard Medical School’s George Daley suggested that it may be time to reconsider the massive amounts of research done over the past several years and look for plausible methods of moving forward.

What to watch: Scientists are cautious about predicting what the impact will be, in part because the details of this claim are thin. However, the debate is heating up and one concern is it will dampen important research.

  • Medical ethicist Jonathan Moreno from the University of Pennsylvania says the situation reminds him of other times in history where there were tremors in the science world, like the death of 18-year-old Jesse Gelsinger in 1999 from a gene therapy trial that led to years of diminished research.

The bottom line: The alarm over what could be next is real. But scientists hope the current debate will promote consensus on firm limits and promote transparency.

Go deeper:

SOURCE

From: Andrew Freedman <andrew.freedman@axios.com>

Date: Thursday, November 29, 2018 at 5:33 PM

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

Subject: Axios Science: About that climate report — Gene editing takes a foreboding step — Building in harms’ way

He Jiankui spoke at the second international summit on human genome editing in Hong Kong. (Alex Hofford/EPA-EFE/Shutterstock)

CRISPR-baby scientist faces the music

The scientist who claims to have helped produce the first people born with edited genomes faced a tough crowd yesterday at a gene-editing summit in Hong Kong. He Jiankui gave a 20-minute talk about his unpublished work in animals and humans before opening a 40-minute Q&A session (watch it here). He faced difficult questions about the ethics of his work and his choice to keep it mostly under wraps until after the babies were born, and left many unanswered.

Meanwhile, prominent geneticist George Church is one of the few scientists who seem to be looking on the bright side of He’s controversial claim. “Let’s be quantitative before we start being accusatory,” Church told Science. “As long as these are normal, healthy kids it’s going to be fine for the field and the family.”

Nature | 9 min read & Science | 6 min read

Read more: Genome-edited baby claim provokes international outcry

SOURCE

From: Nature Briefing <briefing@nature.com>

Reply-To: Nature Briefing <briefing@nature.com>

Date: Thursday, November 29, 2018 at 12:18 PM

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

Subject: CRISPR-baby scientist faces the music at gene-editing summit

See

Sam Baker 
SAVE

The ethical red flags of genetically edited babies

Driving the news: Chinese scientist He Jiankui announced Sunday night that a pair of twin girls had been born from embryos he modified using the gene-editing tool known as CRISPR.

  • He hasn’t provided solid proof, but if it‘s true, it would be the first time the technology has been used to engineer a human.

What they’re saying: The inventors of CRISPR technology did not seem pleased with the development — one called for a moratorium on implantation edited embryos into potential mothers.

  • “I hope we will be more cautious in the next thing we try to do, and think more carefully about when you should use technology versus when you could use technology,” said Jessica Berg, a bioethicist at Case Western Reserve University.

Between the lines: Several specific factors in He’s work sent up ethical red flags.

  • Many scientists had assumed that, when this technology was first used in humans, it would edit out mutations tied to a single gene that were certain to cause a child pain and suffering once it was born — essentially, as a last resort.
  • But He used CRISPR to, as he put it, “close a door” that HIV could have one day traveled through. That has prompted some speculation that this project was more about testing the technology than serving an acute medical need.
  • “That should make us very uneasy about the whole situation,” Berg said. “Of all the things to have started with, it does make you a little suspicious about this particular choice.”

The intrigue: There’s a lot we still don’t know about He’s work, and that’s also contributing to an attitude of skepticism.

  • How many embryos did he edit and implant before these live births?
  • How will he know it worked? As the children age, they’ll likely have their blood drawn and those samples will be exposed to HIV in a lab, but researchers aren’t going to tell them to go out and have unprotected sex or use intravenous drugs — another reason HIV seems like an odd starting place for human gene editing.
  • How did this even happen? The university where He worked said he was on leave, and Chinese officials have said he’s under investigation. But gene editing is a pretty hard thing to freelance.

The other side: He defended his work in a video message, saying, “I understand my work will be controversial but I believe families need this technology and I’m willing to take the criticism for them.”

  • “Their parents don’t want a designer baby, just a child who won’t suffer from a disease which medicine can now prevent,” He said.

Yes, but: Now that this threshold may have been crossed, attempts to create “designer babies” — within the limitations of what CRISPR can do — probably aren’t far off, some experts fear.

  • There are “likely to be places that are less regulated than others, where people are going to attempt to see what they can do,” Berg said. “I wouldn’t say everything in the world has changed now, but it’s certainly the next step.”
SOURCE

https://www.axios.com/genetic-editing-baby-china-ethics-controversy-b33f8414-8b83-445c-bad5-d8407f8841f4.html

https://pharmaceuticalintelligence.com/2018/11/26/jennifer-doudna-and-npr-science-correspondent-joe-palca-several-interviews/

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LIVE 2018 The 21st Gabay Award to LORENZ STUDER, Memorial Sloan Kettering Cancer Center, contributions in stem cell biology and patient-specific, cell-based therapy

Posted in cell-based therapy, Competition in regenerative stem cell science, Patient-centered Medicine, Personalized and Precision Medicine & Genomic Research, stem cell biology and patient-specific, Stem Cells for Regenerative Medicine on October 9, 2018| Leave a Comment »

LIVE 2018 The 21st Gabay Award to LORENZ STUDER, Memorial Sloan Kettering Cancer Center, contributions in stem cell biology and patient-specific, cell-based therapy

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

AWARD LECTURE

Tue., Oct. 9, 2018
4:00 PM
Shapiro Campus Center Theater
Brandeis University

CURRENT WINNER

lorenzstuder.jpgLORENZ STUDER

MACARTHUR FELLOWS PROGRAM

Lorenz Studer

Stem Cell Biologist | Class of 2015

Pioneering a new method for large-scale generation of dopaminergic neurons that could provide one of the first treatments for Parkinson’s disease and prove the broader feasibility of stem cell–based therapies for other neurological disorders.

https://www.macfound.org/fellows/947/

118 publications on PubMed

https://www.ncbi.nlm.nih.gov/pubmed/?term=LORENZ+STUDER

 

PRESIDING

Dagmar Ringe Professor of Biochemistry, Chemistry and Rosenstiel Basic Medical Sciences Research Center

WELCOME

Lisa Lynch Provost and Maurice B. Hexter Professor of Social and Economic Policy Brandeis University

 

RESPONSE Lorenz Studer, MD Director, Center for Stem Cell Biology Memorial Sloan Kettering Cancer Center Member, Developmental Biology Program Memorial Sloan Kettering Cancer Center

Fully defined protocol for all ectodermal lineage

  • Nervous system: Forebrain, Midbrain, Spinal cord:
  • CNS lineage to PNS Lineage
  • Excitatory cortical neurons
  • cortical interneurons Astrocytes
  • microglia
  • Age-reset disease – late-onset during reprogramming – Is age reversible?
  • Loss of age-related markers
  • iPSC-derived cells yield stage cell upon differentiation
  • In vitro differentiation techniques: 2D Directed Differentiation 3D- Organoids
  • Graded MORPHOGEN SIGNALING
  • DOXYCYLINE: ISHH-ORGANIZER – 5 discrete forebrain regions
  • Building Human brain cells in 2D and in 3D
  • Organized cells –>>>  directed organoids –>> Organized Organoids
  • Parkinson, 1817 – Essay on Shaky Palsy (Niagrostaterial pathway)
  • Genetics and related dysfunction: affecting PD
  • Charckot, 1889
  • PD – new approach following drugs and deep brain stimulation failure in advanced disease: Fetal tissue transplant trials: Fetal Grafting
  • graft-induced dyskinesia
  • Long term, 15 years positive effects
  • Stem-cell-based regenerative therapy could transform PD therapy
  • 1995  Fetal DA neuron grafting for PD in Switzerland
  • 1998 – midbrain stem cell derived DA neuron
  • 200-2003 – Stem cell in brain implantation in WashDC
  • 2011 – Behavioral assays that are restored in mice
  • Optogenetics: manipulating – Light on the brain – control animal’s neurons
  • MOA of Graft function
  • Dopamine neurons – Stratium area of the human brain
  • From bench to bedside – WNT boost enhances EN1 expression
  • Neuron melanin induction
  • Manufacturing and QA testing: GMP – Off the shelf Allogenic Product
  • 1,000 human dose equivalents
  • cryopreserve
  • MSK-DA01 is highly enriched for mDA neuron precursors without detectable hESC Contaminants
  • FDA feedback and final steps to IND – PRE-IND MEETING: 2014, 2016
  • GLP STUDIES:
  • TUMORIGENICITY, BIODISTRIBUTION AND TOXISITY
  • HISTOLOGY OF FINAL PRODUCT
  • CLINICAL TRIAL DESIGN – STEM-PD – MSK and Weill Cornell Medicine
  • HLA expression is absent in edited iPSC with expression of HLA-E to block NK clearance
  • FUTURE: CRISPR
  • ATLaS-PD – assessing the longitudinal Symptoms/signs to moderate of severe stage
  • Development of a new PD therapy from Pluripotent Stem Cells
  • BlueRock Therapeutics – MSK-PD – Start up – $240Million funding
  • Stem cell based dopamine therapy for PD
  • Immunosuppression for 12 months
  • defined levodopa response > 45% improvement
  • Conclusions
  • Cell banks for clinical trials
  • NY state Stem cell science consortia

http://www.brandeis.edu/rosenstiel/images/pdfs/gabbay21program.pdf

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