Search

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. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) have been demonstrated to play important roles in cancer progress. However, the roles in hepatocellular carcinoma (HCC) are still unclear. Here, we found has_circRNA_001306 (circ_1306) was up‐regulated in HCC tissues and cell lines. Knockdown the expression circ_1306 significantly suppressed HCC cell proliferation and induced the cell apoptosis in vitro and in vivo. Furthermore, we identified circ_1306 could up‐regulate the expression of CDK16 by sponging miR‐584‐5p. The expression of miR‐584‐5p was decreased, and the expression of CDK16 was increased in HCC tissues and cell lines. Meanwhile, either knockdown of miR‐584‐5p or overexpression of CDK16 could suppress the HCC cell proliferation. In vivo, overexpression of miR‐584‐5p or knockdown of circ_1306 could inhibit the expression of CDK16, and suppress tumour growth. Altogether, our findings suggested that circ_1306 could promoter HCC progress by miR‐584‐5p/CDK16 axis, which provided a novel marker for HCC diagnosis and treatment. [ABSTRACT FROM AUTHOR]