Radiation Combined with Immunotherapy

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Andrew Sharabi, MD, PhD
Assistant Professor of Radiation Medicine
Director, Radiation Medicine Core Facility
Scientific Advisor, San Diego Center for Precision Immunotherapy


This project will elucidate the benefits of combining stereotactic radiation therapy with checkpoint blockade immunotherapy for cancer. Importantly, these key findings will be directly translated into clinical trials incorporating radiation and immunotherapy to improve outcomes for patients with locally-advanced and metastatic disease. Funding for this project was generously provided by the Kimmelman Family.

The Need
Radiation therapy is a critical part of the curative treatment for multiple different cancer types. Over the past decade there has been a revolution in radiation oncology due to the ability to deliver highly focused precision radiation termed stereotactic radiation or stereotactic body radiation therapy (SBRT) to any area of the body. In comparison to conventional radiation therapy which can last 5-7 weeks, stereotactic radiation allows radiation oncologists to deliver curative doses of radiation in one to five treatments total with minimal toxicity. However, the technology to deliver these precision radiation treatments in research models has lagged behind the clinical capabilities. Small animal irradiators are a revolutionary advancement which accelerate the translation of preclinical radiation studies into clinical patient care. Thus there is a critical need to study the benefits of stereotactic radiation when compared to standard radiation techniques, specifically in combination with cancer immunotherapy.

The Opportunity
Andrew Sharabi, MD, PhD, is a physician-scientist, immunologist, and board certified Radiation Oncologist. He trained at Johns Hopkins where he was one of the first to discover that stereotactic radiation can synergize with anti-PD-1 immunotherapy. His team is investigating how stereotactic body radiation therapy can modulate the tumor microenvironment to enhance antigen presentation and T-cell infiltration into tumors. Additionally Dr. Sharabi will be investigating whether site of irradiation or irradiation of tumor-associated draining lymph nodes (DLN), impacts adaptive immune responses when combined with anti-PD-1 and anti-CTLA-4 immunotherapies. The ultimate goal of this project is to develop this combinatorial therapy to improve tumor control and development of long-term memory immune responses.

The Impact
These efforts will establish the benefits of combining stereotactic radiation therapy with checkpoint blockade immunotherapy for cancer. Importantly, these key findings will be directly translated into clinical trials incorporating radiation and immunotherapy to improve outcomes for patients with locally-advanced and metastatic disease.