Department of Pancreatic Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
Department of Gastroenterology, Wuhan Third Hospital, Wuhan, China.
Liver Int. 2021 May;41(5):1033-1043. doi: 10.1111/liv.14771. Epub 2021 Jan 7.
While CAR-T therapy has successfully treated haematological malignancies, it has proved sub-optimal for solid tumours. The main limitation is the inability of CAR-T cells to infiltrate and then proliferate within tumours.
We co-expressed IL-7 and PH20, a type of hyaluronidase, with CAR targeting GPC3 (G3CAR-7 × 20). We test the anti-tumour ability in vitro and in vivo. Moreover the capacity of infiltration and proliferation of G3CAR-7 × 20 was measured.
We found (G3CAR-7 × 20) exhibited better proliferation in vivo and in vitro than G3CAR, reduced the level of apoptosis after stimulation by tumour cells, and maintained the memory phenotype of CAR-T cells. G3CAR-7 × 20 also increased the ability of CAR-T cells to infiltrate tumour tissue.
co-expressed IL-7 and PH20 may significantly enhance the efficacy of targeted GPC3 CAR-T cells in solid tumours treatment.
嵌合抗原受体 T 细胞（CAR-T）疗法已成功治疗血液系统恶性肿瘤，但在实体瘤中的疗效并不理想。主要限制在于 CAR-T 细胞无法渗透到肿瘤中并在其中增殖。
我们共表达白细胞介素 7（IL-7）和 PH20（一种透明质酸酶）与针对 GPC3 的 CAR（G3CAR-7×20）。我们在体外和体内测试了抗瘤能力。此外，还测量了 G3CAR-7×20 的渗透和增殖能力。
我们发现（G3CAR-7×20）在体内和体外的增殖能力均优于 G3CAR，降低了肿瘤细胞刺激后的细胞凋亡水平，并保持了 CAR-T 细胞的记忆表型。G3CAR-7×20 还增加了 CAR-T 细胞渗透肿瘤组织的能力。
共表达 IL-7 和 PH20 可能显著增强针对 GPC3 的 CAR-T 细胞在实体瘤治疗中的疗效。
