Abstract A02: A pathogen boosted adoptive cell transfer immunotherapy to treat solid tumors

Despite the remarkable success in treating hematological malignancies, adoptive cell transfer (ACT) still faces several challenges in treating solid tumor. The main stumbling blocks include insufficient quantity of tumor-specific T cells for transfer, impaired migration of transferred T cells into the tumor and the immunosuppressive microenvironment within the tumor. To overcome these problems, we designed an innovative approach that not only overcomes immunosuppression, but also induces robust anti-tumor T cell responses in the tumor. We first genetically engineered dual-specific CD8 T cells that can recognize both a tumor associated antigen and a bacterial antigen in vitro. Then, we treated tumor-bearing mice with ACT using a small number of the dual-specific CD8 T cells. This was accompanied by intratumoral injection of a low dose of the bacteria, which was sufficient to break local immunosuppression. The dual-specific CD8 T cells expanded robustly and migrated to the tumor bed in response to the infection. At the same time, the second TCR of these effector CD8 T cells recognized tumor antigen and executed effector function, causing tumor regression. As a result of this enhanced anti-tumor effects, 60% of the treated mice successfully eradicated their solid tumor at the primary site. Our approach not only overcomes immunosuppression, but also recruits robust anti-tumor T cell responses to the tumor. Overall, our study harnesses the power of multiple arms of the immune system with promising translational value, which can be used to target many types of solid tumors. Citation Format: Gang Xin, David Schauder, Aimin Jiang, Nikhil Joshi, Weiguo Cui. A pathogen boosted adoptive cell transfer immunotherapy to treat solid tumors. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr A02.