Preclinical testing of CAR T cells in zebrafish xenografts

Abstract

Engineered chimeric antigen receptor T cells (CAR T cells) have emerged as a promising immunotherapy for cancer and have proven to be effective for B cell malignancies. Currently, great efforts are undertaken to expand the application of CAR T cells to other cancer entities, to increase the efficacy of CAR T cell-mediated killing of cancer cells and to reduce possible side effects of CAR T cell therapy. This creates a need for preclinical models to test the many emerging novel CAR designs. Traditionally, mouse xenograft models are applied to investigate the efficacy of CAR T cells in vivo. Here, we describe a complementing xenograft protocol for testing CAR T cells against human leukemia cells in zebrafish embryos. The embryonic zebrafish xenograft promises to be a fast and cost-efficient model and particularly offers live imaging opportunities of CAR T cell distribution and killing of cancer cells in vivo.

Keywords: CAR T cells; Cancer; Leukemia; Preclinical testing; Xenotransplantation; Zebrafish.