Read the first part of the interview, in which Sharma explains how the platform benefits the mission of the Moon Shots Program, how the Moon Shots benefit her research and what’s unique about her immunotherapy investigations.
In part two, Sharma discusses the platform’s support of MD Anderson investigators working to expand the impact of immune-based treatments. She also covers advances made by the platform, including a greater understanding of immune checkpoint therapies' complex biology and important collaborations with the Melanoma Moon Shot™ and Prostate Cancer Moon Shot™.
Q: What successes have you realized so far in your immunotherapy research?
Sharma: Our team has done path-changing work to advance our understanding of the complex biology of immune checkpoint therapies. For example, we conducted studies of melanoma in mouse models to discover that anti-CTLA4 and anti-PD1 therapies are driven by distinct cellular biology. Anti-CTLA4 therapy leads to expansion of a specific population of T cells that have been shown to associate with favorable responses. In contrast, anti-PD1 therapy does not induce this population.
A recent publication also reports a possible new immunotherapy target in pancreatic cancer, which has been particularly resistant to immune checkpoint blockade thus far. Working with the Pancreatic Cancer Moon Shot™, we were able to identify that the immune checkpoint VISTA is overexpressed on immune cells that infiltrated pancreatic tumors, and we hope to exploit this in future clinical studies.
We’ve also made significant progress in changing care for our patients. Our research led to the approval of anti-PD1 therapy for treating patients with metastatic renal cell carcinoma, which is now the standard of care.
Through a collaboration with Dr. Jennifer Wargo and the Melanoma Moon Shot™, we found that we can predict the response to anti-CTLA4 and/or anti-PD-1 early in the treatment of metastatic melanoma, which is vital to delivering the right treatment to the right patient as quickly as possible.
Our findings also have launched clinical trials with the Prostate Cancer Moon Shot™. One is investigating a combination of immune checkpoint therapies for treating castrate-resistant prostate cancer, which has not benefitted previously from immunotherapies, and another is directing patients to specific treatments based on whether their tumors are immunologically “hot” or “cold.”
We’re very excited to learn the results of these studies and potentially bring new treatments to those patients very much in need of them.
Q: What’s the future look like for the immunotherapy platform?
Sharma: To this point, most immunotherapy has been considered a last-line treatment for refractory cancer. We would like to see immunotherapy applied earlier in the course of treatment, in combination with traditional therapies such as radiation, chemotherapy, and small-molecule drugs. At this stage, immunotherapies could have a synergistic effect, potentially eliminating cancer throughout the body.
The effects of traditional therapies on the cancer immune response are complex. They can be positive, such as when chemo or radiation kills tumor cells and releases tumor antigens, initiating a cancer immune response. However, they also can be negative, such as when high-dose radiation eliminates antigen presenting cells in the tumor microenvironment.
We have the techniques and knowledge in place to comprehensively profile the effects of these treatments on the cancer immune response. The knowledge gained from this analysis will help us to design and initiate new clinical trials, develop novel therapies, and define trials based on patient responses. Ultimately, we hope to add immunotherapy to the standard-of-care for many more patients.