Co‐expression of IL‐7 and PH20 promote anti‐GPC3 CAR‐T tumour suppressor activity in vivo and in vitro

Abstract 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.