John A. Glaspy, MD
Immunotherapy has demonstrated efficacy in a number of solid and liquid tumors, and although responses in ovarian cancer have yet to mirror those in other malignancies, John A. Glaspy, MD, explained that, though limited, immunotherapy is not completely inactive.
There are many routes to triggering immunogenicity in ovarian cancer, such as vaccines, epigenetic therapies, and combination strategies, said Glaspy, adding, “Sorting through them is going to be the challenge.”
In an interview during the 2018 OncLive®
State of the Science Summit™ on Ovarian Cancer, Glaspy, professor of medicine, Jonsson Comprehensive Cancer Center (JCCC), director, JCCC Clinical Research Unit and Women's Cancer Research Program, University of California, Los Angeles, discussed challenges and progress with immunotherapy in gynecologic cancers.
OncLive: How has immunotherapy impacted the field of ovarian cancer, if at all?
: Immunotherapy has been an exploding field over the last few years. It's revolutionized the treatment of some cancers, especially melanoma and other skin cancers, lung cancer, bladder cancer, and others. It has not been nearly as effective in the treatment of [patients with] breast cancer and colon cancer. It has been disappointing but not totally inactive in ovarian cancer. The question is, “Is there a way to make it work as well in ovarian cancer as it does in, say, melanoma? If that is possible, what is the path to that?”
We know that the best predictor of immunotherapy’s efficacy is the extent of the mutation in the individual tumor type. If the immune system is going to recognize a cancer as unique, that cancer needs to express an antigen that isn’t expressed on normal cells, called a neoantigen. The chances of any one mutation leading to a neoantigen that will work is very small. You need thousands and thousands of mutations to have a chance of getting some neoantigens. That is probably why the mutational burden of tumors is predictive of response to these agents.
There isn't a way that I'm aware of, or that will be available anytime soon, to make a patient’s tumor have more mutations. The question is, if we think tumor mutational burden (TMB) is the problem with ovarian cancer—which it may be—“How do we make those tumors more immunogenic? How do we introduce neoantigens into them?”
There are a variety of possibilities, including vaccines. Vaccines can be directly injected into tumors, causing them to express cytokines and rendering them more immunogenic. There is a school of thought that radiating a tumor will cause it to break down and make it more likely to find an antigen that will work.