Basic Research in Immune Oncology and Molecular Genomics: Methods to Stimulate Immunity by Alteration of Tumor Antigens
Reporter: Aviva Lev-Ari, PhD, RN
I covered in Real Time the great event organized by Partners HealthCare Innovations
Real Time Coverage and eProceedings of 2016 World Medical Innovation Forum: CANCER, April 25-27, 2016, Westin Hotel, Boston
Here I wish to report on the one Presentation at
LIVE – 8:00 am – 12:00 pm 4/25/2016 – First Look: The Next Wave of Cancer Breakthroughs @2016 World Medical Innovation Forum: CANCER, April 25-27, 2016, Westin Hotel, Boston
by Mark Cobbold, MD, PhD, MGH, Tumor Antigens in Cancer and How to Manipulate Antigens to Stimulate Immunity
which I found to be, as I wrote in Real Time, at the end of the Session:
[MOST IMPORTANT TALK]
- challenges for immuno-oncology (IO)
- Posttranslational NeoAntigens
- tumor — Surfacre MHC
- PTM post-translational modifications — MS
- CRC Surface Phosphopeptides – antigenicity increasing in metastasis
- Re-arming Existing Antibodies
- Re-arming Existing Antibodies for Antigen Modulation
- T cell activation
- Redirecting CMV- specific T cells
Each presenter had 15 minutes, thus, what was captured was minimal. I am providing here few more details based on the material included in the handout distributed to attendees: First Look, The Next Wave of Cancer Breakthroughs, 4/25/2016, 8AM – 12PM
Tumor Antigens in Cancer and How to Manipulate Antigens to Stimulate Immunity
Mark Cobbold, MD, PhD, Center for Cancer Immunology, MGH
Associate Professor of Medicine, HMS
Associate Member of the Broad Institute of Harvard and MIT
QUOTE START
The role of anti-tumor immunity in the protection and control of arising tumors has been an intense focus of research for decades. While it is clear from strong correlative clinical data combined with definitive experimental evidence from mouse models that T-cells mediate this protection; the nature of the antigens targeted remains poorly characterized. Over the past decade, the role of altered-self antigens, termed neoantigens, has become clear. Tumor-specific neoantigens are known to act as targets of spontaneously arising adaptive immunity to cancer and thereby determine the ultimate fate of developing tumors. Nonsynonymous mutations in coding regions of expressed proteins are termed mutational neoantigents and, perhaps critically, are not subject to central tolerance. In cancers with high mutational loads such as non-small cell lung cancer and melanoma CD8+ T-cells can be identified within the tumor against MHC class-I restricted neoantigens in patients responding to immunotherapy. Despite these advance questions remain in the field, for example tumor-resident immunity against mutational neoantigens is typically at a very low frequencies and it is surprising that this magnitude of immunity can be responsible for dramatic reductions in tumor volume. Additionally, some of the tumors with the best clinical responses to immunotherapy have some of the lowest mutational loads for example renal cell carcinoma and leukemia. Hematological malignancies in particular are known to be amongst the most immunogenic cancers. Therefore, it is likely that the antigens in these malignancies derive from other classes of antigens.
Since dysregulation of cell signaling pathways plays a prominent role in cancer, leukemia-specific antigens may derive from the posttranslational modifications (PTMs) associated with aberrant signaling. Indeed, we have previously shown that a number of phosphorylated peptides as potent cancer antigens. Interestingly, immunity to these antigens was seen in healthy donors, but lost in a subset of leukemia patients with poor clinical outcomes and restored after SCT, suggesting a role for these neoantigens in the graft-vs-leukemia response. O-GlcNAcylation is another process involved in the dysregulation of cell signaling pathways in cancer. It functions as a nutrient sensor and regulates numerous cell signaling pathways by blocking and unblocking phosphorylation sites.
QUOTE END
SOURCE
Handout distributed to attendees: First Look, The Next Wave of Cancer Breakthroughs, 4/25/2016, 8AM – 12PM @2016 World Medical Innovation Forum: CANCER, April 25-27, 2016, Westin Hotel, Boston
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