Abstract PR06: Dual-specific T-cells and an indirect vaccine eradicate large solid tumors

Abstract

While immunotherapy can eliminate substantial burdens of some leukemias, the ultimate challenge remains the eradication of large solid tumors and metastases for most cancers. Here we generate dual-specific T-cells expressing a chimeric antigen receptor (CAR) specific for Her2 and a TCR specific for the melanocyte protein (gp100). Injection of T-cells, together with a vaccine that contains a recombinant vaccinia virus expressing gp100, induced durable complete remission of a variety of Her2+ tumors and established metastases, some in excess of 150 mm2, in immunocompetent mice expressing Her2 in normal tissues. Tumor destruction occurred rapidly over seven days and was associated with an extensive infiltrate of T-cells. Mice that had rejected tumors were resistant to rechallenge with the same Her2+ tumor cells, indicating the formation of immune memory. Furthermore, we have established methods to transduce dual-specific T-cells from human peripheral blood with both a TCR specific for gp100 and a CAR for Her2. From as little as 1 ml of human buffy coat, we could generate sufficient numbers of cells for a course of treatment for a patient. The stimulation of gp100 through TCR enhanced the human dual-specific CAR T-cell proliferation, secretion of IFN-γ and killing of Her2+ human cancer cells in vitro. These characteristics were identified to be important for eradicating tumors in the mouse models. Taken together, our data provide valuable information for the development of CAR T-cell therapies for patients with solid cancers and evidence for pursuing a phase I clinical trial. Citation Format: Clare Y. Slaney, Bianca von Scheidt, Phillip K. Darcy, Michael H. Kershaw. Dual-specific T-cells and an indirect vaccine eradicate large solid tumors [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr PR06.