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

Liver Int. 2021 May;41(5):1033-1043. doi: 10.1111/liv.14771. Epub 2021 Jan 7.

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.

Keywords: CAR-T; IL-7; PH20; memory T cell.

MeSH terms

  • Animals
  • Cell Adhesion Molecules / metabolism*
  • Cell Line, Tumor
  • Glypicans
  • Humans
  • Hyaluronoglucosaminidase / metabolism*
  • Immunotherapy, Adoptive*
  • Interleukin-7 / metabolism*
  • Male
  • Mice
  • Neoplasms / therapy*
  • Receptors, Chimeric Antigen*
  • Xenograft Model Antitumor Assays

Substances

  • Cell Adhesion Molecules
  • GPC3 protein, human
  • Glypicans
  • Interleukin-7
  • Receptors, Chimeric Antigen
  • Hyaluronoglucosaminidase
  • hyaluronidase PH-20