To address manufacturing cost and time issues for CAR T cells, Agarwal et al. investigated antitumor potency of CD19 CAR T cells by specifically transducing CD8α+ cells in vivo with lentivirus (CD8-LV). A single IV injection of CD8-LV eliminated CD19+ Nalm-6 tumors in BM and spleens of NSG mice (injected with activated human PBMC) compared to controls. Tumor elimination was due to in vivo generated CAR+ cells, which comprised 5-12% of human CD8+ T cells in BM, spleen, and blood at day 14, compared to 0% of CD8- cells. Unexpectedly, due to their low ex vivo transduction efficiency, some BM CD8α+ NK and NKT cells were also CAR+.
Contributed by Katherine Turner
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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 in vivo generation of human CD19-CAR T cells by targeting CD8(+) cells using lentiviral vectors (LVs). The anti-tumor potency of in vivo 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 in vivo 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 in vivo generated human CAR T cells.