Targeted Antitumor Activity With Recombinant Adeno-associated Virus Secreting PD1 In Mouse Hepatocelluar Carcinoma

Objective: To construct recombinant adeno-associated virus,treat liver cancer and explore its mechanism.Methods: Adeno-associated virus and the gene sequence of the outer segment of PD1 were used to construct recombinant adeno-associated virus.The liver cancer model was established and its anti-tumor effect was observed by observing tumor volume and survival curve.The number of killer T cells was measured by flow cytometry and the number of memory T cells in the spleen was measured.Result:(1)Successfully construct a recombinant virus AAV8-PD1 expressing PD1(AAV8-PD1)by genetic engineering technology.(2)Compared with the three control groups,the tumor volume and tumor weight were significantly decreased in AAV8-PD1 treatment group respectively(P<0.0001).(3)The number of CD8 positive cytotoxic T lymphocyte in the recombinant adeno-associated virus AAV8-PD1 treatment group within tumor tissues was significantly higher than that in the control group.The number of cytotoxic T lymphocyte in each group was AAV8-PD1(6.08%),v GFP(0.33%),a PD1(1.22%)and Mock control group(0.16%)(P<0.001).(4)The number of CD8 positive memory T cells in the spleen in AAV8-PD1 treatment group(25.7%)was more than in controls [20.4%(v GFP),19.7%(a PD1)and 13.4%(Mock),P<0.01].Conclusion:(1)Recombinant adeno-associated virus AAV8-PD1 can stably infect liver tissue and express green fluorescent protein in liver tissue.(2)Recombinant adeno-associated virus AAV8-PD1 significantly inhibited tumor growth in a liver cancer model.(3)The number of cytotoxic T lymphocyte within tumor tissues significantly increase induced by AAV8-PD1.(4)The number of CD8-positive memory T cells in the spleen increase induced by AAV8-PD1.