An RNA vaccine drives expansion and efficacy of claudin-CAR-T cells against solid tumors

Chimeric antigen receptor (CAR)–T cells have shown efficacy in patients with B cell malignancies. Yet, their application for solid tumors has challenges that include limited cancer-specific targets and nonpersistence of adoptively transferred CAR-T cells. Here, we introduce the developmentally regulated tight junction protein claudin 6 (CLDN6) as a CAR target in solid tumors and a strategy to overcome inefficient CAR-T cell stimulation in vivo. We demonstrate that a nanoparticulate RNA vaccine, designed for body-wide delivery of the CAR antigen into lymphoid compartments, stimulates adoptively transferred CAR-T cells. Presentation of the natively folded target on resident antigen-presenting cells promotes cognate and selective expansion of CAR-T cells. Improved engraftment of CAR-T cells and regression of large tumors in difficult-to-treat mouse models was achieved at subtherapeutic CAR-T cell doses.

Source: ScienceNOW - January 22, 2020 Category: Science Authors: Reinhard, K., Rengstl, B., Oehm, P., Michel, K., Billmeier, A., Hayduk, N., Klein, O., Kuna, K., Ouchan, Y., Wöll, S., Christ, E., Weber, D., Suchan, M., Bukur, T., Birtel, M., Jahndel, V., Mroz, K., Hobohm, K., Kranz, L., Diken, M., Kühlc Tags: Immunology reports Source Type: news