Systemic delivery of a TLR7 agonist in combination with radiation primes durable anti-tumor immune responses in mouse models of lymphoma
Menée sur des modèles murins de lymphome à cellules B ou T, cette étude montre qu'un agoniste du récepteur TLR-7, administré par voie systémique, peut, en combinaison avec une radiothérapie, améliorer l'efficacité et la durée de la réponse immunitaire antitumorale
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.