Hi,
I am new to the field of immunology. I am trying to understand the different sources of cancer neoantigens and they can be utilized for immunotherapies. In one of the books, I read that 'tumor-specific neoantigens can be treated as self if they do not cause inflammation'. I guess that's why cancer vaccines etc. are administered with adjuvants. However, what usually causes inflammation in the context of cancer so that the neoantigens are recognized as foreign? Is it due to the rapid growth of the tumor and destruction of neighboring tissue or cancer cell death?
I would appreciate any feedback.
Best,
Martyna
Hi Martyna,
I'm not specialized in cancer vaccines but I recently saw a presentation showing a preclinical study where such a vaccine was more efficacious when it was co-administered with anti-PD-1 mAbs.
Several things should induce inflammation when a cancer appears (e.g. cell proliferation, angiogenesis, tumor-cell migration, etc) but cancer cells often overexpress a PD-1 ligand that interacts with PD-1 surface receptor on effector T cells. Since PD-1 inhibits T cell inflammatory activity, it results in cancer immune evasion.
Blocking PD-1 should restore local inflammatory responses against neoantigens that are not recognized as self-antigens by the immune system. Therefore, a vaccine that targets some neoantigens will be able to kill cancer cells expressing them.
I hope this will be helpful for you
Pierre-Marie
http://www.nature.com/nature/journal/v454/n7203/fig_tab/nature07205_F1.html
https://www.ncbi.nlm.nih.gov/pubmed/21074057
hi
you have chosen very beautiful and interesting area in biology .
The selection of neonatal antigens is a clever choice. But it should be noted that the immune response, even with adjuvant, does not produce efficient immune response .
Perhaps the answer to your question is to find the difference between the Post-translational modification (PTM) of an antigen in a normal and cancerous cell.
Success and congratulations on choosing the right way.
Dear Martyna, you need to look on the literature devoted to DAMPs and alarmins. Here is the review, which is useful to start search. https://www.ncbi.nlm.nih.gov/pubmed/27101817
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