Feeds:
Posts
Comments

Posts Tagged ‘posttranslational modifications (PTMs)’

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

https://pharmaceuticalintelligence.com/2016/04/28/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

https://pharmaceuticalintelligence.com/2016/04/25/live-800-am-1200-pm-4252016-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

Read Full Post »

%d bloggers like this: