St. Anna Children's Cancer Research Institute, Innovative Cancer Models, Vienna, Austria.
St. Anna Children's Cancer Research Institute, Christian-Doppler Laboratory for Next Generation CAR T Cells, Vienna, Austria.
Methods Cell Biol. 2022;167:133-147. doi: 10.1016/bs.mcb.2021.07.002. Epub 2021 Aug 20.
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.
工程化嵌合抗原受体 T 细胞（CAR T 细胞）已成为癌症治疗的一种有前途的免疫疗法，并且已被证明对 B 细胞恶性肿瘤有效。目前，正在努力将 CAR T 细胞的应用扩展到其他癌症实体，以提高 CAR T 细胞介导的杀伤癌细胞的功效并降低 CAR T 细胞治疗的可能副作用。这就需要临床前模型来测试许多新出现的新型 CAR 设计。传统上，应用小鼠异种移植模型来研究 CAR T 细胞在体内的功效。在这里，我们描述了一种互补的异种移植方案，用于在斑马鱼胚胎中测试 CAR T 细胞对人白血病细胞的作用。胚胎斑马鱼异种移植有望成为一种快速且具有成本效益的模型，特别提供了 CAR T 细胞分布和体内杀伤癌细胞的活体成像机会。
