Xingcheng Xiong1, Juanli Xi2, Qian Liu3, Cixiao Wang4, Zeyou Jiang3, Su-Yang Yue5, Lei Shi6, Yuping Rong1. 1. Department of Pancreatic Surgery, Renmin Hospital of Wuhan University, Wuhan, China. 2. Department of Gastroenterology, Wuhan Third Hospital, Wuhan, China. 3. Department of Clinical Laboratory, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China. 4. Nephrology Department II, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China. 5. Department of Gastroenterology, The Affiliated Huai'an Hospital of Xuzhou Medical University, The Second People's Hospital of Huai'an, Huaian, China. 6. Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, China.
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.
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.