Genomic and Immunologic Correlates of Immunotherapy Response and Resistance via Longitudinal Tumor and Extracellular Vesicle (EV) Analysis
Abstract
Scientific Objective: Immunotherapy in the form of checkpoint blocking antibodies is one of the most exciting approaches to cancer disease control as it allows the body’s own immune system to fight tumors. In metastatic melanoma, these approaches can lead to over half of patients responding to the therapy, with a third of patients having no disease progression for many years. There is much excitement about the use of these therapies, but to truly understand these treatments, work is needed to identify why some patients do not respond or stop responding to the therapies and create tools to predict who will or will not get benefit from these treatments. Here, we propose to study individual patients to understand the interaction of multiple pathways that can lead to therapy failure simultaneously. At the same time, we will study these same patients’ blood to create blood tests that can help predict response and guide the use of these drugs in the clinic. Principal Investigator’s (PI’s) career goals in cancer research: Dr. Boland (PI) is an expert in melanoma and immunotherapy, both in the clinic and in the laboratory. She is the Director of the Massachusetts General Hospital (MGH) Melanoma Surgery Program and the Director of the MGH Surgical Oncology Research Laboratories. She is actively combining her clinical practice as a surgical oncologist with her role as a researcher to study tumors and blood from her patients to understand why certain therapies work in some patients and not in others. She is also focused on creating clinically-relevant tools, such as blood-based tests, to guide clinical decision-making. Applicability of the research: While this project is specifically focused on melanoma patients, many other cancer patients are now being treated with these same therapies. This project is focused on understanding why some patients do not benefit from these drugs by studying patient tumors in melanoma. However, the goal is to compare these findings with data generated in other cancer types to understand how this research can be applied more broadly. While tumor studies give us much information on the biology of cancer, they are not feasible in many cases due to the inaccessibility of the tumor for sampling. Therefore, this project also focuses on creating new tools to monitor changes in both the tumor and the immune system from circulating blood. While there are many techniques that are being investigated to monitor the tumor or the immune system in circulation, there are no current techniques to monitor them in parallel. This proposal aims to create a new technique for combined tumor and immune monitoring by using microvesicles that are released into the blood stream by both tumor cells and immune cells. There are many possible clinical uses for a tool such as this: (1) use this technique to select patients that you predict have a high chance of responding to the drug while sparing patients who may not respond to the drug the side-effects of a drug that won’t benefit them, (2) use this tool to monitor the immune system during treatment in order to use the lack of immune signals to guide changing to another therapy before evidence of disease recurrence is present, (3) use this tool to verify no residual tumor and ongoing immune activation in order to decide when to terminate therapy, (4) use this tool to monitor tumor and immune levels to predict immune-related side effects of the drugs. These applications would be of significant value to patients, clinicians, and payers, as it would allow optimal use of therapies selectively in appropriate populations of patients. Military Relevance: While this study is being done in metastatic melanoma, these tools and techniques can easily be broadly applied to other solid tumor types in the future. Our proposal is directly relevant and addresses two topics of importance: immunotherapy and melanoma. It applies specifically to gaps in the detection of disease and/or tre
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 16, 2019
- Source ID
- W81XWH1910143
Entities
People
- Genevieve Boland
Organizations
- Massachusetts General Hospital
- United States Army