Synergy of purine-scaffold TLR7 agonist with doxorubicin on systemic inhibition of lymphoma in mouse model

Abstract

Chemo- and radio-therapy suffer from certain well-recognized drawbacks for lymphoma therapy. Passive immunotherapy with monoclonal antibody has improved outcome for patients with CD20+ B cell lymphoma, but not for T cell lymphoma. Therefore, novel treatment approaches are clearly required for T cell lymphoma. To date, the combined application targeting TLR7, 8 and 9 has established long-term antitumor immunity. We previously synthesized a purine-scaffold TLR7 agonist named GD5. Here, we report that the intratumoral administration of GD5 combined with doxorubicin (DOX), a conventional chemotherapeutic agent in T cell lymphoma. This combined treatment made mice to produce more cytokines in blood, and generate more potent cytotoxic T lymphocyte response, then result in effective eradication of both local and distant tumors in tumor-bearing mice. Our findings demonstrate the potential for enhancing the efficacy of the current standard DOX therapy through combination with TLR7 agonist GD5 to improve antitumor immune responses and provide durable remissions for T cell lymphoma.