Agarwal Shiwani, Weidner Tatjana, Thalheimer Frederic B, Buchholz Christian J
Molecular Biotechnology and Gene Therapy, Paul-Ehrlich-Institut, Langen, Germany.
Frankfurt Cancer Institute, Goethe University, Frankfurt am Main, Germany.
Oncoimmunology. 2019 Oct 10;8(12):e1671761. doi: 10.1080/2162402X.2019.1671761. eCollection 2019.
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 generation of human CD19-CAR T cells by targeting CD8 cells using lentiviral vectors (LVs). The anti-tumor potency of 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 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 generated human CAR T cells.
嵌合抗原受体（CAR）T细胞是当前癌症免疫治疗研究的重点。促进CAR T细胞的产生是首要目标之一。我们最近通过使用慢病毒载体（LVs）靶向CD8细胞，证明了可直接产生人CD19-CAR T细胞。在静脉注射CD19 Nalm-6肿瘤细胞的人PBMC移植的NSG小鼠中评估了所产生的CAR T细胞的抗肿瘤效力。单次注射递送CD19-CAR的靶向CD8的LV足以从骨髓和脾脏中完全消除肿瘤细胞，而对照动物含有高水平的CD19细胞。肿瘤消除归因于所产生的CAR细胞。值得注意的是，这些细胞不仅由T淋巴细胞组成，还包括CAR自然杀伤细胞（NK和NKT）。这是所产生的人CAR T细胞消除肿瘤的首次证明。
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