Localized Chemotherapy Based on Injectable Hydrogel Boosts the Antitumor Activity of Adoptively Transferred T Lymphocytes In Vivo.

Abstract

The adoptive transfer of antigen-specific T cells has been successfully applied in the treatment of hematological malignancies. However, its application in the treatment of solid tumors has been overshadowed by the immunosuppressive tumor microenvironment. In this context, a preprocessing strategy is developed to reprogram the immunosuppressive tumor microenvironment using a thermoresponsive hydrogel loaded with doxorubicin (DOX@Gel). Compared with hydrogel-based chemotherapy alone or adoptive T cell therapy alone, this combination exhibits enhanced anti-tumor efficacy. In addition to the direct killing of tumor cells, the local chemotherapy releases tumor-associated antigens which enhance the proliferation and effector function of endogenous and adoptively transferred T cells. Moreover, DOX@Gel significantly reduces the numbers of both myeloid derived suppressor cells and Tregs in tumor microenvironment. It is suggested that DOX@Gel promotes the efficacy of adoptively transferred T cells against solid tumors, overcoming the key limitations of adoptive T cell therapy.