Local administration of a novel Toll-like receptor 7 agonist in combination with doxorubicin induces durable tumouricidal effects in a murine model of T cell lymphoma

Jiang Zhu, Shiping He, Jie Du, Zhulin Wang, Wang Li, Xianxiong Chen, Wenqi Jiang, Duo Zheng, Guangyi Jin

Conventional chemotherapy and radiotherapy for the treatment of lymphoma have notable drawbacks, and passive immunotherapy using a monoclonal antibody is restricted to CD20-positive B cell lymphoma. Therefore, new treatment types are urgently required, especially for T cell lymphoma. One type of new antitumour therapy is the use of active immunotherapeutic agents, such as agonists of the Toll-like receptors (TLRs), which facilitate the induction of prolonged antitumour immune responses. We have synthesised a novel TLR7 agonist called SZU-101 and investigated the systemic antitumour effect on a murine model of T cell lymphoma in vivo. Here, we report that the intratumoural administration of SZU-101 enhanced the effectiveness of a conventionally used chemotherapeutic agent, doxorubicin (DOX). SZU-101 administration improved tumour clearance in a murine model of T cell lymphoma. The novel combination of intratumourally administered SZU-101 and DOX generated strong cytokine production and enhanced the cytotoxic T lymphocyte response, leading to the eradication of both local and distant tumours in tumour-bearing mice. These findings suggested that combined active immunotherapy can be developed as a promising treatment for T cell lymphoma, which may further improve the effectiveness of the current standard cyclophosphamide, DOX, vincristine and prednisone (CHOP) therapy.