Archive for the ‘BioTechnology – Venture Creation, Venture Capital’ Category

JP Morgan Healthcare Day Two: Thermo Fisher; Qiagen; Danaher; Counsyl; Human Longevity; Adaptive Bio, 10X Genomics and Pacific Biosciences

Posted in BioTechnology - Venture Creation, Venture Capital, Computational Biology/Systems and Bioinformatics, Conference Coverage with Social Media, Gene Regulation, Gene Regulation and Evolution, Genetics & Innovations in Treatment, Genome Biology, Genomic Testing: Methodology for Diagnosis, tagged 10X Genomics Pacific Biosciences, Business News JP Morgan Healthcare Conference Adaptive Biotechnologies Counsyl Danaher Human Longevity JP Morgan Qiagen Thermo Fisher Scientific on January 13, 2016| Leave a Comment »

JP Morgan Healthcare Day Two: Thermo Fisher; Qiagen; Danaher; Counsyl; Human Longevity; Adaptive Bio, 10X Genomics and Pacific Biosciences

Reporter: Aviva Lev-Ari, PhD, RN

 

JPM16 & BTS16: A dour start to biopharma’s big week as stocks feel the pain

By Sy Mukherjee | January 12, 2016

 

BioPharma Dive is here in San Francisco attending the Biotech Showcase 2016 and the 34th Annual JPMorgan Healthcare Conference. The city is swamped with biopharma companies, healthcare firms, investors & VCs, and analysts of all stripes for what has grown to be the biggest week for the life sciences.

But unlike last year, when the industry’s bullishness about 2015 was palpable, the conferences this year got off to a decidedly more downbeat start on Monday. Here are the topline takeaways you need to know from yesterday’s events and presentations.

Biopharma stocks continue to feel the New Year pain

READ MORE @ SOURCE

http://www.biopharmadive.com/news/jpm16-bts16-a-dour-start-to-biopharmas-big-week-as-stocks-feel-the-pain/411935/

GENOMICS in Focus

JP Morgan Healthcare Day Two: Thermo Fisher; Qiagen; Danaher; Counsyl; Human Longevity; Adaptive Bio, 10X Genomics, Pacific Biosciences

Reporters: Staff Reporter @ genomeweb.com

 

 

JP Morgan Healthcare Day Two: Thermo Fisher; Qiagen; Danaher; Counsyl; Human Longevity; Adaptive Bio, 10X Genomics, Pacific Biosciences

Jan 13, 2016

|

Ed Winnick

|

Monica Heger

the_westin_st._francis_hotel_san_francisco.jpg

WikiMedia Commons

SAN FRANCISCO (GenomeWeb) – The 34th Annual JP Morgan Healthcare Conference entered its second day here Tuesday with several life science research tools and diagnostic firms making presentations to investors and other attendees.

The following are capsules from the presentations and breakout sessions of

• Thermo Fisher Scientific,
• Qiagen,
• Danaher,
• Counsyl,
• Human Longevity, and
• Adaptive Biotechnologies.

SEE DETAILS in

SOURCE

https://www.genomeweb.com/business-news/jp-morgan-healthcare-day-two-thermo-fisher-qiagen-danaher-counsyl-human-longevity

10X Genomics, Pacific Biosciences Provide Business Updates at JP Morgan Healthcare Conference

Jan 13, 2016

|

Monica Heger

Among the presenting companies were sequencing technology firms 10X Genomics and Pacific Biosciences. Executives from these firms provided attendees with an update on recently launched products and platforms, and future technology developments.

• 10X Genomics and
• Pacific Biosciences

SEE DETAILS in

SOURCE

https://www.genomeweb.com/sequencing-technology/10x-genomics-pacific-biosciences-provide-business-updates-jp-morgan-healthcare

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Day One at #JPM16: Breakout sessions of 23andMe, Myriad Genetics, Genomic Health, and Alere

Posted in Biomarkers & Medical Diagnostics, BioTechnology - Venture Creation, Venture Capital, Computational Biology/Systems and Bioinformatics, Genome Biology on January 12, 2016| Leave a Comment »

Day One at #JPM16: Breakout sessions of 23andMe, Myriad Genetics, Genomic Health, and Alere

Reporter: Aviva Lev-Ari, PhD, RN

JP Morgan Healthcare Conference, Day One: 23andMe; Myriad Genetics; Genomic Health; Alere

Jan 11, 2016

a GenomeWeb staff reporter

 

the_westin_st._francis_hotel_san_francisco.jpg

Image SOURCE

Wikimedia Commons

 

SAN FRANCISCO (GenomeWeb) – The 34th Annual JP Morgan Healthcare Conference began here Monday with several life science research tools and diagnostic firms making presentations to investors and other attendees.

The following are capsules from the presentations and breakout sessions of 23andMe, Myriad Genetics, Genomic Health, and Alere. Coverage of Illumina’s presentation is available here.

SEE Detailed reports on

• 23andMe;
• Myriad Genetics;
• Genomic Health;
• Alere

https://www.genomeweb.com/business-news/jp-morgan-healthcare-conference-day-one-23andme-myriad-genetics-genomic-health-alere?utm_source=SilverpopMailing&utm_medium=email&utm_campaign=Daily%20News:%20Day%20One%20of%20the%20JP%20Morgan%20Healthcare%20Conference%20%E2%80%93%20Updates%20from%2023andMe,%20Myriad%20Genetics,%20Genomic%20Health,%20and%20Alere%20-%2001/12/2016%2011:20:00%20AM

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TSUNAMI in HealthCare under the New Name Verily.com

Posted in Big Data, BioIT: BioInformatics, BioIT: BioInformatics, NGS, Clinical & Translational, Pharmaceutical R&D Informatics, Clinical Genomics, Cancer Informatics, Biological Networks, Biological Networks, Gene Regulation and Evolution, Biomarkers & Medical Diagnostics, Biomedical Measurement Science, BioTechnology - Venture Creation, BioTechnology - Venture Creation, Venture Capital, Cancer and Current Therapeutics, CANCER BIOLOGY & Innovations in Cancer Therapy, Cancer Informatics, Cancer Prevention: Research & Programs, Cancer Screening, Frontiers in Cardiology and Cardiovascular Disorders, Gene Regulation, Genetics & Innovations in Treatment, Genetics & Pharmaceutical, Genome Biology, Genomic Testing: Methodology for Diagnosis, Global Partnering & Biotech Investment, HealthCare IT, Immuno-Oncology & Genomics, Innovation in Immunology Diagnostics, Intellectual Property, Innovations, Commercialization, Investment in technological breakthrough, International Global Work in Pharmaceutical, Investment in Technological Breakthrough, IP Development by LPBI Group Team, IP Development by LPBI Group Team & Other Organizations, Joint Venture - SBH & M3DP: SOP and Arrangements, LPBI Group, e-Scientific Media, DFP, R&D-M3DP, R&D-Drug Discovery, US Patents: SOPs and Team Management on December 14, 2015| Leave a Comment »

TSUNAMI in HealthCare under the New Name Verily.com

Curator: Aviva Lev-Ari, PhD, RN

 

UPDATED on 6/8/2016

The Tricorder project was announced only 3 months after Google entered the life sciences field, according to the report, and came from the same incubator which rolled out the company’s self-driving car and recently cancelled Google Glass.

Verily CEO Andrew Conrad said the scientific basis for the device was proven upon unveiling in 2014, but experts have presented conflicting views on the reality of such a device, STAT Newsreports.

“What (Verily is) really good at is physical measurements — things like temperature, pulse rate, activity level. They are not particularly good at … the chemical and the biological stuff,” Walt toldSTAT news.

Four former Verily employees said the Tricorder “has been seen internally more as a way to generate buzz than as a viable project,” according to the report.

SOURCE

http://www.massdevice.com/googles-star-trek-tricorder-bid-flops/?spMailingID=9031578&spUserID=MTI2MTQxNTczMjM5S0&spJobID=940786327&spReportId=OTQwNzg2MzI3S0

 

UPDATED on 4/16/2016

SOURCE

http://recode.net/2016/04/13/verily-alphabet-profitable/

Verily, Alphabet’s medical business, is profitable, Sergey Brin tells Googlers

Verily | YouTube

SCIENCE

• 
• By Mark Bergen
• @mhbergen
• EMAIL

April 13, 2016, 2:20 PM PDT

Publicly, Alphabet has said very little about its assortment of companies not named Google.

But internally, Alphabet is a little more forthcoming.

As we reported earlier, Nest CEO Tony Fadell appeared before Google’s all-hands meeting two weeks ago to address recent criticism of his company. During that meeting, Google co-founder and Alphabet exec Sergey Brin also defended another company under the holding conglomerate: Verily, the medical tech unit previously called Google Life Sciences.

Lumped together, Alphabet’s moonshots aren’t making money yet — but Verily is, Brin said.

Verily was the target of a scathing article — in Stat, a medical publication from the Boston Globe — scrutinizing its CEO, Andy Conrad. Several former employees told Stat that Verily suffered a talent exodus due to “derisive and impulsive” leadership by Conrad.

Here’s what Brin said in response at Google’s TGIF meeting:

I have seen a smattering of articles. And, you know, it’s actually sad to see sometimes where it appeared that … former employees or soon-to-be former employees talked to the press. But, anyhow, I can tell you what’s going on with these companies, fortunately. So in Verily’s case, despite a handful of examples, their attrition rate is below Google’s and Alphabet’s as a whole. And also, there are articles that have generally said we are blowing a lot of money and so forth. It’s true that, you know, as whole our Other Bets are not yet profitable, but some of them are, including Verily on a cash basis and increasingly so. So we’re pretty excited about these efforts.

Verily makes money through

• partnerships with pharmaceutical companies — such as Novartis, which is licensing and planning to sell Verily’s smart contact lens — and
• medical institutions.

It is one of three units contributing to the Other Bets total revenue ($448 million) in 2015, along with

• Google Fiber and
• Nest.

As we reported earlier, Nest likely brought in around $340 million of that and Fiber pulled close to $100 million, meaning that Verily’s sales were somewhere around $10 million. During the year, all the moonshot units combined reported operating losses of $3.6 billion.

RELATED

SCIENCE

Verily, Google’s Health Gambit, Is Stacked With Scientists. Now It Needs to Build a Business.

By Mark Bergen, Dec 14, 2015, 3:00 AM PST

Note Brin’s stipulation that Verily’s profit comes on a “cash basis.” That probably means that it’s not making profit on the normal basis, meaning when you take into account total sales minus total costs. But “cash positive” suggests they’re booking sales faster than they’re spending money, which is a positive sign. Companies normally report financials accounting for all costs. And that’s how Alphabet will next week, when it shares first-quarter results for Google and the Other Bets — although we almost certainly won’t see figures on Verily’s profitability.

We reached out to Alphabet and Verily reps for more clarity, but didn’t get any.

SOURCE

http://recode.net/2016/04/13/verily-alphabet-profitable/

 

Original Curation dated 12/14/2015

1. Part 1: Verily in Action
2. Part II: Innovations at a Different Scale: GDE Enterprises – A Case in Point of Healthcare in Focus – Work-in-Progress

12/31/2015 – All time

1. Following this Journal by e-mail subscription: along with X other amazing people
2. views
3. comments
4. Top Post and Pages
5. Click Summaries
6. Posts
7. Categories
8. Tags
9. Top Authors Views

 

Part 1: Verily in Action

They write @ https://verily.com/

When Google[x] embarked on a project in 2012 to put computing inside a contact lens — an immensely challenging technical problem with an important application to health — we could not have imagined where it would lead us. As a life sciences team within Google[x], we were able to combine the best of our technology heritage with expertise from across many fields. Now, as an independent company, Verily is focused on using technology to better understand health, as well as prevent, detect, and manage disease.

Andy Conrad, Ph.D.

Chief Executive OfficerFormerly the chief scientific officer of LabCorp, Andy is a cell biologist with a doctorate from UCLA. He has always been passionate about early detection and prevention of disease: Andy co-founded the National Genetics Institute, which developed the first cost-effective test to screen for HIV in blood supply.

Brian Otis, Ph.D.

Chief Technical OfficerBrian’s team focuses on end-to-end innovation ranging from integrated circuits to biocompatible materials to sensors. He joined Google[x] as founder of the smart contact lens project and now leads our efforts across all hardware and device projects, including wearables, implanted devices, and technology like Liftware.

Jessica Mega, M.D., MPH

Chief Medical OfficerJessica leads the clinical strategy and research team at Verily. She is a board-certified cardiologist who trained and practiced at Massachusetts General Hospital and Brigham and Women’s Hospital. As a faculty member at Harvard Medical School and a senior investigator with the TIMI Study Group, Jessica directed large, international trials evaluating novel cardiovascular therapies.

Linus Upson

Head of EngineeringA long-time Google software engineer, Linus has been a team lead in developing products that now help billions of people worldwide find the information they need on the Internet, including Chrome and Chrome OS. He now oversees our engineering teams.

Tom Stanis

Head of SoftwareTom spent nine years working on core Google products before joining Google[x] in 2014 to work on the Baseline Study. He now leads all our Software projects, including the development of machine learning algorithms for applications ranging from robotic-assisted surgery to diabetes management.

Vikram (Vik) Bajaj, Ph.D.

Chief Scientific OfficerVik’s broad research interests in industry and as a former academic principal investigator have included structural and systems biology, molecular imaging, nanoscience, and bioinformatics. Vik now leads the Science team in research directions related to our mission.

What are the Dimensions of the Tsumani in Healthcare?

• prevention,
• detection,
• management of disease

 

Hardware

• contact lens with an embedded glucose sensor for measuring the glucose in human tears.

Software

• multiple sclerosis, for example, combines wearable sensors with traditional clinical tests
• signals that could lead to new knowledge about the disease and why it progresses differently among individuals.

Clinical

• Constituencies industry, hospitals, government, academic centers, medical societies, and patient advocacy groups
• The Baseline Study is one of these dedicated efforts, a multi-year initiative that aims to identify the traits of a healthy human by closely observing the transition to disease.

Science

• Understand processes that lead to conditions like cancer, heart disease, and diabetes
• computational systems biology platforms and life sciences tools
• bio-molecular nanotechnology for precision diagnostics and therapeutic delivery
• advanced imaging methods for applications ranging from early diagnosis to surgical robotics.

 

FOLLOW the LEADER of Parish in the Tsunami

 

Google[x] searches for ways to boost cancer immunotherapy | Science/AAAS | News

http://news.sciencemag.org/math/2015/01/googlex-searches-ways-boost-cancer-immunotherapy

 

Google Life Sciences and American Heart Association commit $50M to study heart disease | VentureBeat

http://venturebeat.com/2015/11/08/google-life-sciences-and-american-heart-association-commit-50m-to-study-heart-disease/

 

Google Life Sciences Division Is Now Called… Verily?

http://gizmodo.com/google-life-sciences-division-is-now-called-verily-1746729894

 

WIRED: Google’s Verily Is Spinning Off ‘Verb,’ a Secretive Robot-Surgery Startup

Alphabet’s Verily, née Google Life Sciences, has announced its first spinoff, a brand new robot-assisted surgery company.

http://www.wired.com/2015/12/googles-verily-is-spinning-off-verb-a-secretive-robot-surgery-startup/

 

Google Life Sciences Rebrands as Verily under Alphabet – Fortune

Vik Bajaj, CSO

http://fortune.com/2015/12/08/google-alphabet-verily/

Verily, I Swear, Google Life Sciences debuts a New Name

By CHARLES PILLER  DECEMBER 7, 2015

http://www.statnews.com/2015/12/07/verily-google-life-sciences-name/

 

Alphabet’s Life Sciences Business Has a New Name: Verily

CONOR DOUGHERTY DECEMBER 7, 2015 8:22 PM

http://bits.blogs.nytimes.com/2015/12/07/alphabets-life-sciences-business-has-a-new-name-verily/?_r=0 

Why biomedical superstars are signing on with Google Tech firm’s ambitious goals and abundant resources attract life scientists.

Erika Check Hayden 21 October 2015

http://www.nature.com/news/why-biomedical-superstars-are-signing-on-with-google-1.18600

 

GOOGLE LIFE SCIENCES MAKES DIABETES ITS FIRST BIG TARGET

• AUTHOR: KLINT FINLEY.KLINT FINLEY BUSINESS

• DATE OF PUBLICATION: 08.31.15.08.31.15

• TIME OF PUBLICATION: 6:01 PM.6:01 PM

http://www.wired.com/2015/08/google-life-sciences-makes-diabetes-first-big-target/

 

GOOGLE WON THE INTERNET. NOW IT WANTS TO CURE DISEASES

• AUTHOR: DAVEY ALBA.DAVEY ALBA BUSINESS

• DATE OF PUBLICATION: 08.19.15.08.19.15

• TIME OF PUBLICATION: 7:00 AM.7:00 AM

http://www.wired.com/2015/08/google-won-internet-now-wants-cure-diseases/

 

Google Reveals Health-Tracking Wristband

Caroline Chen and Brian Womack

June 23, 2015 — 9:30 AM EDT

http://www.bloomberg.com/news/articles/2015-06-23/google-developing-health-tracking-wristband-for-health-research

 

Google Moves to the Operating Room in Robotics Deal With J&J

ALISTAIR BARR and JOSEPH WALKER

http://blogs.wsj.com/digits/2015/03/27/google-moves-to-the-operating-room-in-robotics-deal-with-jj/

 

Google, Biogen Seek Reasons for Advance of Multiple Sclerosis

Caroline Chen

January 27, 2015 — 9:00 AM EST

http://www.bloomberg.com/news/articles/2015-01-27/google-biogen-seek-reasons-for-advance-of-multiple-sclerosis

 

Google’s Newest Search: Cancer Cells

Google X Team Hopes to Develop Nanoparticles to Provide Early Detection of Cancer, Other Diseases

ALISTAIR BARR and RON WINSLOW

Updated Oct. 29, 2014 11:17 a.m. ET

http://www.wsj.com/articles/google-designing-nanoparticles-to-patrol-human-body-for-disease-1414515602

 

A Spoon That Shakes To Counteract Hand Tremors

Updated May 14, 201411:43 AM ET

INA JAFFE

http://www.npr.org/sections/health-shots/2014/05/13/310399325/a-spoon-that-shakes-to-counteract-hand-tremors

 

Google’s New Moonshot Project: the Human Body

Baseline Study to Try to Create Picture From the Project’s Findings

ALISTAIR BARR

Updated July 27, 2014 7:24 p.m. ET

http://www.wsj.com/articles/google-to-collect-data-to-define-healthy-human-1406246214

 

Novartis Joins With Google to Develop Contact Lens That Monitors Blood Sugar

MARK SCOTT JULY 15, 2014

http://www.nytimes.com/2014/07/16/business/international/novartis-joins-with-google-to-develop-contact-lens-to-monitor-blood-sugar.html

 

Google[x] searches for ways to boost cancer immunotherapy

Jon Cohen

15 January 2015 6:25 am

http://news.sciencemag.org/math/2015/01/googlex-searches-ways-boost-cancer-immunotherapy

 

SOURCE

https://verily.com/

Part II: Innovations at a Different Scale: GDE Enterprises

A Case in Point of Healthcare in Focus –

Work-in-Progress

 

 

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CRISPR Gene Editing Trial

Posted in Auditory and vision, BioTechnology - Venture Creation, Venture Capital, Clinical & Translational, Clinical Genomics, CRISPR/Cas9 & Gene Editing, Curation, tagged CRISPR, familial blindness, gene editing on November 10, 2015| Leave a Comment »

CRISPR Gene Editing Trial

Larry H Bernstein, MD, FCAP, Curator

LPBI

 

CRISPR Gene Editing to Be Tested on People by 2017

http://www.technologyreview.com/news/543181/crispr-gene-editing-to-be-tested-on-people-by-2017-says-editas/

 

A biotechnology company says it will test advanced gene-engineering methods to treat blindness.

By Antonio Regalado on November 5, 2015

 

Editas CEO Katrine Bosley

The biotechnology startup Editas Medicine intends to begin tests of a powerful new form of gene repair in humans within two years.

Speaking this week at the EmTech conference in Cambridge, Massachusetts, Editas CEO Katrine Bosley said the company hopes to start a clinical trial in 2017 to treat a rare form of blindness using CRISPR, a groundbreaking gene-editing technology.

If Editas’s plans move forward, the study would likely be the first to use CRISPR to edit the DNA of a person.

CRISPR technology was invented just three years ago but is so precise and cheap to use it has quickly spread through biology laboratories. Already, scientists have used it to generate genetically engineered monkeys, and the technique has stirred debate over whether modified humans are next (see “Engineering the Perfect Baby”).

Editas is one of several startups, including Intellia Therapeutics and CRISPR Therapeutics, that have plans to use the technique to correct DNA disorders that affect children and adults. Bosley said that because CRISPR can “repair broken genes” it holds promise for treating several thousand inherited disorders caused by gene mistakes, most of which, like Huntington’s disease and cystic fibrosis, have no cure.

Editas, which had not previously given a timeline for an initial human test of CRISPR, will try to treat one form of a rare eye disease called Leber congenital amaurosis, which affects the light-receiving cells of the retina.

The condition Editas is targeting affects only about 600 people in the U.S., says Jean Bennet, director of advanced retinal and ocular therapeutics at the University of Pennsylvania’s medical school. “The target that they have selected is fantastic; it has all the right characteristics in terms of making a correction easily,” says Bennett, who isn’t involved in the Editas study.

Children with LCA are born seeing only large, bright shapes, and infants are diagnosed when they don’t look into their mother’s eyes or react to colorful balloons. Their poor vision can progress to “stone cold blindness where everything is black,” says Bennett.

Editas picked the disease in part because it is relatively easy to address with CRISPR, Bosley said. The exact gene error is known, and the eye is easy to reach with genetic treatments. “It feels fast, but we are going at the pace science allows,” she said. There are still questions about how well gene-editing will work in the retina and whether side effects could be caused by unintentional changes to DNA.

Editas plans to deliver the CRISPR technology as a gene therapy. The treatment will involve injecting into the retina a soup of viruses loaded with the DNA instructions needed to manufacture the components of CRISPR, including a protein that can cut a gene at a precise location. Bosley said in order to treat LCA, the company intends to delete about 1,000 DNA letters from a gene called CEP290 in a patient’s photoreceptor cells.

After the edit, preliminary lab experiments show, the gene should function correctly again. Bosley said Editas still needs to test the approach further in the lab and in animals before a human study starts.

Editas was created by venture capital funds including Third Rock Ventures in 2013 and was cofounded by scientists including Feng Zhang of the MIT/Harvard Broad Institute. It has raised more than $160 million in capital, allowing it to pursue ideas for several treatments simultaneously, Bosley said.

Although the Editas study could be the first for CRISPR in humans, it wouldn’t be the first clinical study of gene editing. An older method called zinc fingers is already in testing to treat HIV infection by the biotechnology company Sangamo Biosciences. But the versatility and ease with which CRISPR can change DNA means it may outpace earlier approaches.

Theoretically, gene editing could be used to repair broken genes in any part of the body. But in practice it is difficult to make DNA repairs in most cell types, such as brain cells. The eye is an exception because doctors can inject treatment directly under the retina.

There is already a gene-therapy treatment for one form of LCA in late-stage clinical testing by Philadelphia biotech Spark Therapeutics, says Bennett, who helped develop that treatment. In that case, an entire, healthy version of a gene is being added to eye cells. Typically, gene therapy can only add genes, not edit them.

LCA has several different genetic causes, and standard gene therapy won’t work for the form of the disease Editas is looking at. That is because the required gene, CEP290, is too big to fit inside a virus, says Bennett, and so there is no easy way to add it.

By targeting an exceptionally rare illness, Editas may have an easier time getting a treatment tested and approved. However, the eventual cost of such a treatment could be extraordinarily high, given the small number of people who would need it. Bennett says only around 3,000 Americans have LCA, and about 20 percent of those have the form being targeted by Editas.

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Humanized Mice May Revolutionize Cancer Drug Discovery

Posted in BioTechnology - Venture Creation, BioTechnology - Venture Creation, Venture Capital, Cancer and Current Therapeutics, CANCER BIOLOGY & Innovations in Cancer Therapy, Monoclonal Immunotherapy, Patents, Pharmaceutical Drug Discovery, Pharmacodynamics and Pharmacokinetics, tagged animal models of disease, Cancer - General, Cancer immunology, Cancer immunotherapy, Conditions and Diseases, Food and Drug Administration, health, humanized mice, immunomodulatory, Monoclonal antibodies, oncology, patient derived xenograft, preclinical testing, research, science on October 9, 2015| Leave a Comment »

Humanized Mice May Revolutionize Cancer Drug Discovery

Curator: Stephen J. Williams, Ph.D.

Word Cloud by Zach Day

Decades ago cancer research and the process of oncology drug discovery was revolutionized by the development of mice deficient in their immune system, allowing for the successful implantation of human-derived tumors. The ability to implant human tumors without rejection allowed researchers to study how the kinetics of human tumor growth in its three-dimensional environment, evaluate potential human oncogenes and drivers of oncogenesis, and evaluate potential chemotherapeutic therapies. Indeed, the standard preclinical test for antitumor activity has involved the subcutaneous xenograft model in immunocompromised (SCID or nude athymic) mice. More detail is given in the follow posts in which I describe some early pioneers in this work as well as the development of large animal SCID models:

Heroes in Medical Research: Developing Models for Cancer Research

The SCID Pig: How Pigs are becoming a Great Alternate Model for Cancer Research

The SCID Pig II: Researchers Develop Another SCID Pig, And Another Great Model For Cancer Research

This strategy (putting human tumor cells into immunocompromised mice and testing therapeutic genes and /or compounds) has worked extremely well for most cytotoxic chemotherapeutics (those chemotherapeutic drugs with mechanisms of action related to cell kill, vital cell functions, and cell cycle). For example the NCI 60 panel of human tumor cell lines has proved predictive for the chemosensitivity of a wide range of compounds.

• The NCI-60 panel has been used by the Developmental Therapeutics Program (DTP) of the U.S. National Cancer Institute (NCI) to screen >100,000 chemically defined compounds plus a large number of natural product extracts for anticancer activity since 1990 [1-3]
• Expression (microarray data) with bioinformatic strategies can use efficacy in one cell type to predict efficacy in cell types not in the panel in A strategy for predicting the chemosensitivity of human cancers and its application to drug discovery however in Coombes, Wang and Baggerly in Genomic Signatures on the NCI60 cell lines DO NOT predict patient response to chemotherapy, and [5] where the authors could not reproduce the results in [4] and discussed in Putting Oncology Patients at Risk and a RETRACTED paper in [6] relying on miRNA signatures.

Even though the immunocompromised model has contributed greatly to the chemotherapeutic drug discovery process. using these models to develop the new line of immuno-oncology products has been met with challenges three which I highlight below with curated database of references and examples.

From a practical standpoint development of a mouse which can act as a recipient for human tumors yet have a humanized immune system allows for the preclinical evaluation of antitumoral effect of therapeutic antibodies without the need to use neutralizing antibodies to the comparable mouse epitope,   thereby reducing the complexity of the study and preventing complications related to pharmacokinetics.

Champions Oncology Files Patents for Use of PDX Platform in Immune-Oncology

Hackensack, NJ – August 17, 2015 – Champions Oncology, Inc. (OTC: CSBR), engaged in the development of advanced technology solutions and services to personalize the development and use of oncology drugs, today announced that it has filed two patent applications with the United States Patent and Trademark Office (USPTO) relating to the development and use of mice with humanized immune systems to test immune-oncology drugs and therapeutic cancer vaccines.

Dr. David Sidransky, the founder and Chairman of Champions Oncology commented, “Drug development ‎in the immune-oncology space is fundamentally changing our approach to cancer treatment. These patents represent potentially invaluable tools for developing and personalizing immune therapy based on cutting edge sequence analysis, bioinformatics and our unique in vivo models.”

Joel Ackerman, Chief Executive Officer of Champions Oncology stated, “Developing intellectual property related to our Champions TumorGraft® platform has been an important component of strategy. The filing of these patents is an important milestone in leveraging our research and development investment to expand our platform and create proprietary tools for use by our pharmaceutical partners. We continue to look for additional revenue streams to supplement our fee-for-service business and we believe these patents will help us capture more of the value we create for our customers in the future.”

The first patent filing covers the methodology used by the Company to create a mouse model, containing a humanized immune system and a human tumor xenograft, which is capable of testing the efficacy of immune-oncology agents, both as single agents and in combination with anti-neoplastic drugs. The second patent filing relates to the detection of neoantigens and their role in the development of anti-cancer vaccines.

Keren Pez, Chief Scientific Officer, explained, “In the last few years, there has been a significant increase in cancer research that focuses on exploring the power of the human immune system to attack tumors. However, it’s challenging to test immune-oncology agents in traditional animal models due to the major differences between human and murine immune systems. The Champions ImmunoGraft™ platform has the unique ability of mimicking a human adaptive immune response in the mice, which allows us to specifically evaluate a variety of cancer therapeutics that modulate human immunity.

“Therapeutic vaccines that trigger the immune system to mount a response against a growing tumor are another area of intense interest. The development of an effective vaccine remains challenging but has an outstanding curative potential. Tumors harbor mutations in DNA that result in the translation of aberrant proteins. While these proteins have the potential to provoke an immune response that destructs early-stage cancer development, often the immune response becomes insufficient. Vaccines can trigger it by proactively challenging the system with these specific mutated peptides. Nevertheless, developing anti-cancer vaccines that effectively inhibit tumor growth has been complicated, partially due to challenges in finding the critical mutations, among others difficulties. With the more recent advances in genome sequencing, it’s now possible to identify tumor-specific antigens, or neoantigens, that naturally develop as an individual’s tumor grows and mutates,” she continued.

Traumatic spinal cord injury in mice with human immune systems.

Carpenter RS, Kigerl KA, Marbourg JM, Gaudet AD, Huey D, Niewiesk S, Popovich PG.

Exp Neurol. 2015 Jul 17;271:432-444. doi: 10.1016/j.expneurol.2015.07.011. [Epub ahead of print]

Inflamm Bowel Dis. 2015 Jul;21(7):1652-73. doi: 10.1097/MIB.0000000000000446.

Use of Humanized Mice to Study the Pathogenesis of Autoimmune and Inflammatory Diseases.

Koboziev I¹, Jones-Hall Y, Valentine JF, Webb CR, Furr KL, Grisham MB.

Author information

Abstract

Animal models of disease have been used extensively by the research community for the past several decades to better understand the pathogenesis of different diseases and assess the efficacy and toxicity of different therapeutic agents. Retrospective analyses of numerous preclinical intervention studies using mouse models of acute and chronic inflammatory diseases reveal a generalized failure to translate promising interventions or therapeutics into clinically effective treatments in patients. Although several possible reasons have been suggested to account for this generalized failure to translate therapeutic efficacy from the laboratory bench to the patient’s bedside, it is becoming increasingly apparent that the mouse immune system is substantially different from the human. Indeed, it is well known that >80 major differences exist between mouse and human immunology; all of which contribute to significant differences in immune system development, activation, and responses to challenges in innate and adaptive immunity. This inconvenient reality has prompted investigators to attempt to humanize the mouse immune system to address important human-specific questions that are impossible to study in patients. The successful long-term engraftment of human hematolymphoid cells in mice would provide investigators with a relatively inexpensive small animal model to study clinically relevant mechanisms and facilitate the evaluation of human-specific therapies in vivo. The discovery that targeted mutation of the IL-2 receptor common gamma chain in lymphopenic mice allows for the long-term engraftment of functional human immune cells has advanced greatly our ability to humanize the mouse immune system. The objective of this review is to present a brief overview of the recent advances that have been made in the development and use of humanized mice with special emphasis on autoimmune and chronic inflammatory diseases. In addition, we discuss the use of these unique mouse models to define the human-specific immunopathological mechanisms responsible for the induction and perpetuation of chronic gut inflammation.

J Immunother Cancer. 2015 Apr 21;3:12. doi: 10.1186/s40425-015-0056-2. eCollection 2015.

Human tumor infiltrating lymphocytes cooperatively regulate prostate tumor growth in a humanized mouse model.

Roth MD¹, Harui A¹.

Author information

Abstract

BACKGROUND:

The complex interactions that occur between human tumors, tumor infiltrating lymphocytes (TIL) and the systemic immune system are likely to define critical factors in the host response to cancer. While conventional animal models have identified an array of potential anti-tumor therapies, mouse models often fail to translate into effective human treatments. Our goal is to establish a humanized tumor model as a more effective pre-clinical platform for understanding and manipulating TIL.

METHODS:

The immune system in NOD/SCID/IL-2Rγnull (NSG) mice was reconstituted by the co-administration of human peripheral blood lymphocytes (PBL) or subsets (CD4+ or CD8+) and autologous human dendritic cells (DC), and animals simultaneously challenged by implanting human prostate cancer cells (PC3 line). Tumor growth was evaluated over time and the phenotype of recovered splenocytes and TIL characterized by flow cytometry and immunohistochemistry (IHC). Serum levels of circulating cytokines and chemokines were also assessed.

RESULTS:

A tumor-bearing huPBL-NSG model was established in which human leukocytes reconstituted secondary lymphoid organs and promoted the accumulation of TIL. These TIL exhibited a unique phenotype when compared to splenocytes with a predominance of CD8+ T cells that exhibited increased expression of CD69, CD56, and an effector memory phenotype. TIL from huPBL-NSG animals closely matched the features of TIL recovered from primary human prostate cancers. Human cytokines were readily detectible in the serum and exhibited a different profile in animals implanted with PBL alone, tumor alone, and those reconstituted with both. Immune reconstitution slowed but could not eliminate tumor growth and this effect required the presence of CD4+ T cell help.

CONCLUSIONS:

Simultaneous implantation of human PBL, DC and tumor results in a huPBL-NSG model that recapitulates the development of human TIL and allows an assessment of tumor and immune system interaction that cannot be carried out in humans. Furthermore, the capacity to manipulate individual features and cell populations provides an opportunity for hypothesis testing and outcome monitoring in a humanized system that may be more relevant than conventional mouse models.

Methods Mol Biol. 2014;1213:379-88. doi: 10.1007/978-1-4939-1453-1_31.

A chimeric mouse model to study immunopathogenesis of HCV infection.

Bility MT¹, Curtis A, Su L.

Author information

Abstract

Several human hepatotropic pathogens including chronic hepatitis C virus (HCV) have narrow species restriction, thus hindering research and therapeutics development against these pathogens. Developing a rodent model that accurately recapitulates hepatotropic pathogens infection, human immune response, chronic hepatitis, and associated immunopathogenesis is essential for research and therapeutics development. Here, we describe the recently developed AFC8 humanized liver- and immune system-mouse model for studying chronic hepatitis C virus and associated human immune response, chronic hepatitis, and liver fibrosis.

PMID:

25173399

[PubMed – indexed for MEDLINE]

PMCID:

PMC4329723

Free PMC Article

• · Images from this publication.See all images (3)Free text

Immune humanization of immunodeficient mice using diagnostic bone marrow aspirates from carcinoma patients.

Werner-Klein M, Proske J, Werno C, Schneider K, Hofmann HS, Rack B, Buchholz S, Ganzer R, Blana A, Seelbach-Göbel B, Nitsche U, Männel DN, Klein CA.

PLoS One. 2014 May 15;9(5):e97860. doi: 10.1371/journal.pone.0097860. eCollection 2014.

From 2015 AACR National Meeting in Philadelphia

LB-050: Patient-derived tumor xenografts in humanized NSG mice: a model to study immune responses in cancer therapy Sunday, Apr 19, 2015, 3:20 PM – 3:35 PM Minan Wang1, James G. Keck1, Mingshan Cheng1, Danying Cai1, Leonard Shultz2, Karolina Palucka2, Jacques Banchereau2, Carol Bult2, Rick Huntress2. 1The Jackson Laboratory, Sacramento, CA; 2The Jackson Laboratory, Bar Harbor, ME

References

1. Paull KD, Shoemaker RH, Hodes L, Monks A, Scudiero DA, Rubinstein L, Plowman J, Boyd MR. J Natl Cancer Inst. 1989;81:1088–1092. [PubMed]
2. Shi LM, Fan Y, Lee JK, Waltham M, Andrews DT, Scherf U, Paull KD, Weinstein JN. J Chem Inf Comput Sci. 2000;40:367–379. [PubMed]
3. Monks A, Scudiero D, Skehan P, Shoemaker R, Paull K, Vistica D, Hose C, Langley J, Cronise P, Vaigro-Wolff A, et al. J Natl Cancer Inst. 1991;83:757–766. [PubMed]
4. Potti A, Dressman HK, Bild A, et al. Genomic signatures to guide the use of chemotherapeutics. Nat Med. 2006;12:1294–1300. [PubMed]
5. Baggerly KA, Coombes KR. Deriving chemosensitivity from cell lines: forensic bioinformatics and reproducible research in high-throughput biology. Ann Appl Stat. 2009;3:1309–1334.
6. Carlson, B. Putting Oncology Patients at Risk Biotechnol Healthc. 2012 Fall; 9(3): 17–21.
7. Salter KH, Acharya CR, Walters KS, et al. An Integrated Approach to the Prediction of Chemotherapeutic Response in Patients with Breast Cancer. Ouchi T, ed. PLoS ONE. 2008;3(4):e1908. NOTE RETRACTED PAPER

Other posts on this site on Animal Models, Disease and Cancer Include:

Heroes in Medical Research: Developing Models for Cancer Research

Guidelines for the welfare and use of animals in cancer research

Model mimicking clinical profile of patients with ovarian cancer @ Yale School of Medicine

Vaccines, Small Peptides, aptamers and Immunotherapy [9]

Immunotherapy in Cancer: A Series of Twelve Articles in the Frontier of Oncology by Larry H Bernstein, MD, FCAP

Mouse With ‘Humanized Version’ Of Human Language Gene Provides Clues To Language Development

The SCID Pig: How Pigs are becoming a Great Alternate Model for Cancer Research

The SCID Pig II: Researchers Develop Another SCID Pig, And Another Great Model For Cancer Research

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