Department of Hematology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, PR China.
Department of Research and Development, Nanjing Aide Institute of Immunotherapy, Nanjing 211808, PR China.
Immunotherapy. 2019 Aug;11(12):1043-1055. doi: 10.2217/imt-2019-0017. Epub 2019 Jul 3.
Chimeric antigen receptor-engineered T (CAR-T) cells have gained huge success in treating hematological malignancies, yet the CD3ζ-based CAR-T therapies have not shown comparable clinical benefits in solid tumors. We designed an alternative chimeric immunoreceptor in which a single-chain variable fragment was fused to the transmembrane-cytoplasmic domains of triggering receptor expressed on myeloid (TREM1), which may show potent antitumor activity. To generate TREM1/DNAX activation protein of 12 kDa (Dap12)-based CAR-T cells, TREM1 along with DAP12 was transduced into T cells. Results: TREM1/Dap12-based CAR-T cells showed more lysis and a similar antitumor effect in mouse models compared with CD19BBζ CAR-T cells. In this study, we designed a TREM1/Dap12-based CAR, which was not reported previously and demonstrated that TREM1/Dap12-based CAR-T cells had potent antitumor activity and
嵌合抗原受体工程化 T（CAR-T）细胞在治疗血液恶性肿瘤方面取得了巨大成功，但基于 CD3ζ 的 CAR-T 疗法在实体瘤中并未显示出可比的临床获益。我们设计了一种替代的嵌合免疫受体，其中将单链可变片段融合到表达于髓样细胞上的触发受体（TREM1）的跨膜-胞质结构域中，这可能显示出强大的抗肿瘤活性。为了生成基于 TREM1/DNAX 激活蛋白 12kDa（Dap12）的 CAR-T 细胞，将 TREM1 与 DAP12 转导到 T 细胞中。结果：与 CD19BBζ CAR-T 细胞相比，基于 TREM1/Dap12 的 CAR-T 细胞在小鼠模型中显示出更强的裂解和相似的抗肿瘤作用。在这项研究中，我们设计了一种以前未报道过的基于 TREM1/Dap12 的 CAR，并证明基于 TREM1/Dap12 的 CAR-T 细胞具有强大的抗肿瘤活性。
