Monday, December 30, 2019

Combination Immunotherapies Offer New Hope for Chemotherapy-Resistant Ovarian Cancer Patients

This is another example of how your tax dollars are working to find cures for particularly deadly types of ovarian cancer.

The Congressionally Directed Medical Research Program (CDMRP) awards $20 million dollars each year for research into ovarian cancer. But each year, Congress has to allocate this money and we continue to hope that in 2020, this research will again be funded.

I have had the privilege and honor to have served  in 2016, 2017 and 2019 as a consumer advocate to award these grants. Although consumer advocates and other members of the panel are never at liberty to discuss individual applications for funding, each year, CDMRP posts on their website, the results of those who have received funding. You can find out more about this by following this link.

In the meantime, here is an article about the oncolytic viruses used in immunotherapy in the treatment of OC. As many of our readers know, immunotherapy is not consistently effective in treating OC. Research by Dr. Dmitry Zamarin out of Sloan Kettering, may shed light on why that is...

Immunotherapy has emerged as a promising approach for ovarian cancer treatment. It enables patients’ immune systems to target cancer cells, and it may be effective where other chemotherapy and radiation have failed. Dr. Dmitriy Zamarin’s research focuses on understanding the mechanisms of immunotherapy in cancer with the hope of identifying new treatments for ovarian cancer patients. To facilitate a career as an independent investigator with a focus in immunotherapy and ovarian cancer, Dr. Zamarin sought support from the Ovarian Cancer Academy. In fiscal year 2015 (FY15), he received an Ovarian Cancer Academy – Early-Career Investigator Award, and with its support, he has investigated biomarkers indicating response or resistance to immunotherapies and developed novel immunotherapeutic ovarian cancer treatment strategies. Impressively, Dr. Zamarin’s research has resulted in a phase II clinical trial focusing on a treatment for ovarian cancer patients that are resistant to standard therapies.
With support from the FY15 award Dr. Zamarin found potential benefits for the use of immunotherapies in ovarian cancer patients, but also noticed limitations. When investigating the use of Programmed Cell Death Receptor 1 (PD-L1) inhibitor drugs, which block the receptors that enable cancer cells to evade the body’s immune response, Dr. Zamarin noted some success in ovarian cancer patients, but the responses were variable, as some patients did not respond to treatment. Dr. Zamarin also researched another type of immunotherapy that has recently emerged: oncolytic viruses (OVs). These molecules selectively target and infect tumor cells, marking them for destruction by the body’s immune system without harming normal tissue. What’s more, in addition to killing injected tumors, OVs induce destruction of distant tumors through the body’s generation of an anti-tumor immune response. Dr. Zamarin determined that OVs increased tumor cell death by the immune system; however, this success was limited by the tumor’s continued expression of PD-L1, which interfered with tumor cell death. 
Based on these results, Dr. Zamarin hypothesized that the application of PD-L1 inhibitors with OVs could prove to be a more effective treatment in ovarian cancer patients. By combining OVs and PD-L1 inhibitors, enhanced activation of the immune response to the tumor, along with tumor regression, was promoted in animal models, an effect that was not seen with either treatment alone. This exciting finding led Dr. Zamarin and colleagues to develop a phase II clinical trial to test the therapeutic combination of an OV, ONCOS-102, and PD-L1 inhibitor, durvalumab, in patients with ovarian cancer that has developed resistance to standard therapies. This trial is currently ongoing. 
Along the same lines, Dr. Zamarin and colleagues are studying whether activation of anti-tumor immune responses using anti-cancer vaccines could boost the efficacy of PD-L1 inhibitors. They have conducted a combination phase II trial of TPIV200, a vaccine targeting folate receptor, with the PD-L1 inhibitor, durvalumab, in patients that failed to show response to standard ovarian cancer treatment. Twenty-seven women with advanced ovarian cancer were enrolled in the trial. Post-immunotherapy follow-up showed an increase in patient survival, suggesting improved clinical benefit from the combination immunotherapy and warranting further exploration of the combined treatment. 
Resistance to chemotherapy is a major problem for women with advanced ovarian cancer, and alternative treatments are desperately needed. Dr. Zamarin’s research into a novel combined immunotherapy provides hope for women in the advanced stages of this disease.

This article was reposted from the CDMRP website.

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