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

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 x 20). We test the anti-tumour ability in vitro and in vivo. Moreover the capacity of infiltration and proliferation of G3CAR-7 x 20 was measured. Result: We found (G3CAR-7 x 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 x 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.

Automated summary

Co-expression of IL-7 and PH20 significantly enhances the proliferation of G3CAR-7 x 20 in vitro and in vivo, reduces apoptosis levels after stimulation by tumour cells, and increases the ability of CAR-T cells to infiltrate tumour tissue.