1. Co-expression of IL-7 and PH20 promote anti-GPC3 CAR-T tumour suppressor activity in vivo and in vitro.
- Author
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Xiong X, Xi J, Liu Q, Wang C, Jiang Z, Yue SY, Shi L, and Rong Y
- Subjects
- Animals, Cell Line, Tumor, Glypicans, Humans, Male, Mice, Xenograft Model Antitumor Assays, Cell Adhesion Molecules metabolism, Hyaluronoglucosaminidase metabolism, Immunotherapy, Adoptive, Interleukin-7 metabolism, Neoplasms therapy, Receptors, Chimeric Antigen
- 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., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2021
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