<i>In vivo</i> generated human CAR T cells eradicate tumor cells

Abstract

Chimeric antigen receptor (CAR) T cells are in prime focus of current research in cancer immunotherapy. Facilitating CAR T cell generation is among the top goals. We have recently demonstrated direct <i>in vivo</i> generation of human CD19-CAR T cells by targeting CD8⁺ cells using lentiviral vectors (LVs). The anti-tumor potency of <i>in vivo</i> generated CAR T cells was assessed in human PBMC-transplanted NSG mice carrying i.v. injected CD19⁺ Nalm-6 tumor cells. A single injection of CD8-targeted LV delivering CD19-CAR was sufficient to completely eliminate the tumor cells from bone marrow and spleen, whereas control animals contained high levels of CD19⁺ cells. Tumor elimination was due to <i>in vivo</i> generated CAR⁺ cells. Notably, these were not only composed of T lymphocytes but also included CAR⁺ natural killer cells (NK and NKT). This is the first demonstration of tumor elimination by <i>in vivo</i> generated human CAR T cells.