Systemic delivery of a TLR7 agonist in combination with radiation primes durable antitumor immune responses in mouse models of lymphoma

Passive immunotherapy with monoclonal antibodies has improved outcome for patients with B cell malignancies although many still relapse and little progress has been made with T cell malignancies. Novel treatment approaches are clearly required in this disease setting. There has been much recent interest in developing therapeutic approaches to enhance anti-tumor immune responses by using novel immunomodulatory agents in combination with "standard" of care treatments. Here, we report that intravenous administration of the TOLL-like receptor (TLR)-7 agonist, R848 in combination with radiation therapy (RT) leads to the long standing clearance of tumor in T and B cell lymphoma bearing mice. In combination, TLR7 / RT therapy leads to the expansion of tumor antigen-specific CD8+ T cells and improved survival. Furthermore those mice that achieve long-term clearance of tumor following TLR7 / RT therapy are protected from subsequent tumor rechallenge by the generation of a tumor-specific memory immune response. Our findings demonstrate the potential for enhancing the efficacy of conventional cytotoxic anti-cancer therapy through combination with a systemically administered TLR7 agonist to improve anti-tumor immune responses and provide durable remissions.