4. (MSK & Genocea Bio. http://www.genocea.com GNCA/$130mm MktCap) 4-2-17 #632 “Genome-scale neoantigen screening using ATLAS prioritizes candidate antigens for immunotherapy in a NSCLC patient”
Neoantigens have flipped PS and makes PS Targeting patents astronomical in value.
Microsoft all over this with MSK SU2C etc...and now it is very clear that Roger must step down from the CEO position because how can he just now on this leap into Biomarkers with Microsoft data analytics able to sift thru the PS Targeting data / Biomarkers....
How foolish will Roger be when he knows his reputation is on the line as evidence continues to emerge that shows all are after PS Targeting Biomarkers
Shared cancer neoantigens: Making private matters public
Christopher A. Klebanoff, Jedd D. Wolchok
DOI: 10.1084/jem.20172188 | Published December 21, 2017 ... ...
Time and again, cancer immunotherapists have unfortunately fallen prey to chasing peptide “ghosts”: highly avid T cells which recognize peptide-pulsed targets that nevertheless fail to recognize HLA-matched, antigen expressing tumor cells. Chheda et al. (2018) avoided this potential pitfall by providing multiple lines of evidence that their candidate epitope is processed, presented, and displayed on the surface of DMG cancer cells. First, the authors used a highly sensitive mass spectrometry-based assay (Bassani-Sternberg et al., 2016) to characterize the peptides bound to MHC molecules isolated directly from DMG cell lines. Using this technique, they identified a variant of the 10-mer mutant peptide only in cells harboring the H3.3K27M mutation but not cells with WT H3.3. Second, using a series of DMG cell lines that all possess the H3.3K27M mutation but are variable in HLA-A2 expression, the authors showed that T cells transduced with the H3.3K27M-specific TCR only recognize HLA-A2+ tumor cells. In an elegant series of reversion experiments, the authors subsequently demonstrated that transduction of HLA-A2 into an HLA-A2- H3.3K27M+ DMG cell line enabled T cell recognition while an anti–HLA-A2 antibody blocked recognition. Critically, additional experiments demonstrated that HLA-A2+ tumor cell lines that were WT for H3.3 were not recognized. This suggests that engineered T cells might be able to distinguish between healthy tissues and tumor cells. Finally, the authors tested whether systemically administered T cells engineered with the mutation-specific TCR treat H3.3K27M+ tumor cells injected within the intracranial cavity of immune-deficient mice. Whereas tumor growth was unabated in mice receiving mock-transduced T cells relative to a saline control, animals receiving TCR engineered cells had a protracted arrest of tumor growth.
Collectively, these data describe an exciting and eminently translatable discovery of a novel “public” neoantigen (see figure). The H3.3K27M26-35 epitope now joins the ranks of other recently uncovered “public” neoantigens resulting from hotspot mutations in driver oncogenes. For example, a series of immunogenic KRAS hotspot mutation–specific epitopes have also been reported which are restricted by HLA-C*08:02 and HLA-A*11:01 (Tran et al., 2016; Wang et al., 2016). Clinically, knowledge of “public” neoantigens could be used to boost what appears in a limited number of tested patients to be a preexisting T cell response using various vaccination approaches. Indeed, this approach using an H3.3K27M26-35 peptide vaccine in combination with the immune-adjuvant Poly-ICLC is now already under way (NCT02960230). It remains to be seen, however, whether any T cell vaccine is potent enough to induce cancer regression in patients with metastatic cancer even if this exceptional class of antigens is targeted (Klebanoff et al., 2011). As suggested by proof-of-concept experiments in the current manuscript, an alternative approach could be to genetically redirect a patient’s T cells to recognize a “public” neoantigen through introduction of a TCR followed by adoptive T cell transfer. The first clinical trial to test this concept in HLA-A*11:01+ patients with cancers harboring the KRAS G12V hotspot mutation has recently been initiated (NCT03190941), and it is possible that the TCR described by Chheda et al. (2018) may rapidly follow suit. Time will tell what the ultimate utility of “public” neoantigens will be. There are ample reasons to believe, however, that they will help democratize the potential benefits of targeting cancer neoantigens to a far greater number of patients more efficiently and rapidly than would otherwise be the case. ... ... http://jem.rupress.org/content/early/2017/12/20/jem.20172188
Dream Team Leader Benjamin Greenbaum, PhD Assistant Professor Department of Genetics & Genomic Sciences, Medicine, Oncological Sciences, and Pathology Icahn School of Medicine at Mount Sinai
Dream Team Co-Leader Vinod Balachandran, MD Assistant Attending Surgeon, Hepatopancreatobiliary Service Member, David M. Rubenstein Center for Pancreatic Cancer Research Member Researcher, Parker Institute for Cancer Immunotherapy Memorial Sloan Kettering Cancer Center
Member Marta Luksza, PhD Assistant Professor Department of Oncological Sciences Icahn School of Medicine at Mount Sinai
Member Eileen M. O’Reilly, MD Associate Director for Clinical Research David M. Rubenstein Center for Pancreatic Cancer Research
Member Jedd Wolchok, MD, PhD Lloyd J. Old/Virginia and Daniel K. Ludwig Chair in Clinical Investigation Chief, Melanoma & Immunotherapeutics Service Associate Director, Ludwig Center for Cancer Immunotherapy Memorial Sloan Kettering Cancer Center
Collaborators
Nina Bhardwaj, MD, PhD Professor, Department of Medicine Director of Immunotherapy Ward Coleman Chair in Cancer Research Icahn School of Medicine at Mount Sinai
Collaborator Curtis Callan, PhD James S. McDonnell Distinguished University Professor of Physics Princeton University
Collaborator Timothy Chan, MD, PhD PaineWebber Chair in Cancer Genetics Director, Immunogenomics and Precision Oncology Platform Member, Human Oncology & Pathogenesis Program Vice Chair, Department of Radiation Oncology Director, Translational Oncology Division Memorial Sloan Kettering Cancer Center
Collaborator Jennifer Chayes, PhD Distinguished Scientist and Managing Director Microsoft Research for Boston and New York City Microsoft Corporation
Collaborator Simona Cocco, PhD Directrice de Recherche, Centre National de la Recherche Scientifique Laboratoire de Physique Statistique Ecole Normale Supérieure
Collaborator Jeffrey Drebin, MD, PhD Chair, Department of Surgery Memorial Sloan Kettering Cancer Center
Collaborator Anthony Gill, MD Staff Specialist, Dept of Anatomical Pathology Chairman of Australian Pancreatic Genome Initiative and Head of Pancreatic Cancer Research Group at the Garvan Institute of Medical Research Professor of Surgical Pathology, University of Sydney
Collaborator Sharon Gillet Principal Program Manager Microsoft Research, New England & New York City
Collaborator Christine Iacobuzio-Donahue, MD, PhD Attending, Department of Pathology, Director, MSKCC Medical Donation Program Director, Cancer Genomics for the David M. Rubenstein Center for Pancreatic Cancer Research Affiliate Member, Human Oncology and Pathogenesis Program
Collaborator Dmitry Krotov, PhD Member, Simons Center for Systems Biology Institute for Advanced Study
Collaborator John Langford, PhD Principal Researcher Microsoft Research
Collaborator Lester Mackey, PhD Researcher Microsoft Research
Collaborator Taha Merghoub, PhD Assistant Attending Lab Member Co-director, Ludwig Collaborative Laboratory and the Swim Across America Laboratory Memorial Sloan Kettering Cancer Center
Collaborator Rémi Monasson, PhD Professor Chargé de Cours Ecole Polytechnique Directeur de Recherche, Centre National de la Recherche Scientifique
Collaborator Thierry Mora, PhD Researcher Laboratoire de Physique Statistique Ecole Normale Supérieure
Collaborator Vasilis Syrgkanis, PhD Researcher Microsoft Research
Collaborator Aleksandra Walczak, PhD Permanent Researcher Laboratoire de Physique Théorique Ecole Normale Supérieure
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ADDING MULTIMEDIA Stand Up To Cancer Announces $11M Collaborative, Multi-Disciplinary Research Program; Microsoft Will Bring Power of AI to Investigate Immune System Response to Cancers “Convergence” Teams of Life Scientists, Bioengineers and Microsoft Machine Learning Experts to Investigate New Cancer Therapies
Lustgarten Foundation and Society for Immunotherapy of Cancer (SITC) Provide Key Support
January 30, 2018 10:08 PM Eastern Standard Time SANTA MONICA, Calif.--(BUSINESS WIRE)--Stand Up To Cancer (SU2C) announces today a “Convergence 2.0” research initiative that awards $11 million to seven multi-disciplinary research teams to investigate immune system response to cancers. The multi-institutional teams being announced today at SU2C’s Scientific Summit draw from the nation’s top academic research centers and will have access to Microsoft Research’s experts in machine learning and artificial intelligence.
“Our first convergence research cohort, announced in 2016, established the effectiveness of a broad multidisciplinary approach for creating models for how cancer grows and reacts to treatment” ... ...
Now I officially believe 100% CEO Renegade Roger Lias is mentally unstable IF he does not allow Pergrine Pharmaceuticals ...now CDMO, to continue R&D research with Dr Jedd Wolchok MSK etc which is so damn vital to increase the so called residual value he states, and Roger has no clue it seems.....
**Through the support from SEAN PARKER, Stand Up To Cancer (SU2C) and the Cancer Research Institute (CRI) formed an Immunology Research Dream Team dedicated to cancer immunology: “Immunologic Checkpoint Blockade & Adoptive Cell Transfer in Cancer Therapy.” The Immunotherapy Dream Team is focused on 2 approaches for this translational cancer research project, which will unite laboratory & clinical efforts towards the immunological treatment, control, and prevention of cancer. The 1st is investigating blockades (by inhibitory molecules called “checkpoints”) of T lymphocytes’ inhibitory receptors, which block immune responses; and the use of antibodies to remove the checkpoints, once again allowing white blood cells called T lymphocytes to kill the cancer cells. Second, the Immunotherapy Dream Team is pursuing multiple Adoptive Cell Transfer (ACT) approaches, which increase immunity.” DREAM TEAM LEADERSHIP: 10 scientists, incl. MSKCC’s Jedd D. Wolchok & Michel Sadelain. http://parker.org/initiatives/immunotherapy
