IL-7 和 PH20 的共表达促进了体内和体外抗 GPC3 CAR-T 肿瘤抑制活性。
Co-expression of IL-7 and PH20 promote anti-GPC3 CAR-T tumour suppressor activity in vivo and in vitro.
机构信息
Department of Pancreatic Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
Department of Gastroenterology, Wuhan Third Hospital, Wuhan, China.
出版信息
Liver Int. 2021 May;41(5):1033-1043. doi: 10.1111/liv.14771. Epub 2021 Jan 7.
BACKGROUND
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.
METHOD
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.
RESULT
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.
CONCLUSION
co-expressed IL-7 and PH20 may significantly enhance the efficacy of targeted GPC3 CAR-T cells in solid tumours treatment.
背景
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。
方法
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。
结果
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。
结论
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。
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