Newswise — New Brunswick, N.J. – October 24, 2018 – Can the combination of radiation therapy with an oncolytic virus treatment better boost the body’s immune response to melanoma than either treatment on its own? Investigators from Rutgers Cancer Institute of New Jersey further explored that question in work presented as part of a poster session at the American Society for Radiation Oncology (ASTRO) Annual Meeting taking place this week in San Antonio, Texas.
The work’s lead author Shang-Jui Wang, MD, medical resident at Rutgers Robert Wood Johnson Medical School, and Bruce G. Haffty, MD, FASTRO, professor and chair, Department of Radiation Oncology at Rutgers Cancer Institute, Rutgers Robert Wood Johnson Medical School and Rutgers New Jersey Medical School who is another author on the work, share more on the team’s findings.
Q: Why is this topic important to explore?
A: We know that radiation treatment can eradicate cancer cells and can manipulate cells in the tumor microenvironment. A herpes-derived oncolytic virus known as talimogene laherparepvec (T-VEC) recently approved by the U.S. Food and Drug Administration for the treatment of melanoma also elicits antitumor immunogenic effects. However, either modality alone is rarely sufficient to overcome the immunosuppressive nature of tumor microenvironment in the clinical setting. We wanted to explore if it would be more effective in the eradication of melanoma by combining these two treatments.
Q: How was the study structured and what did you find?
A: The study was performed in both melanoma cell lines and in vivo models. We found that by combining radiation and T-VEC treatment together, eradication of tumor cells was more effective in vitro and in vivo. Not only did combination treatment with radiation and T-VEC enhance killing of the treated tumors in in vivo models, it also elicited systemic antitumor response against untreated tumors in the same models and prolonged their survival.
To understand the workings behind this phenomenon, we delved into its mechanism and demonstrated that the synergy between radiation and T-VEC is indeed mediated by the immune system. We showed that with combination treatment, tumors harbor a greater number of infiltrated immune cells, which may aid in the elimination of cancer cells. When cytotoxic CD8+ T-cells, a critical population of antitumor immune cells, were depleted from tumor-harboring in vivo models, treatment with radiation and T-VEC became significantly less effective. Using cutting-edge screening technologies, we were able to identify a cytokine molecule, interleukin-1-alpha (IL-1α), as one of the key players in mediating the therapeutic synergy of radiation and T-VEC. Finally, we were able to successfully test the efficacy of this combination treatment in patient melanoma specimens in the presence of the patient’s own immune system using in vivo models, and thereby, providing evidence that this treatment strategy has the potential to be applied clinically.
Q: What are the implications of these findings?
A: This data provides preclinical evidence of the efficacy of combined radiation and T-VEC treatment against melanoma and establishes its underlying immune mechanism. Further studies are underway to better characterize the complex immunomodulatory effect of radiation and T-VEC. Our promising results may warrant an early phase clinical trial to assess safety and efficacy of combining radiation and T-VEC in locally advanced or metastatic melanoma patients.