OBJECTIVETo study the immunoprotective effect of IL-2 and B7-1 gene co-transfected liver cancer vaccine on hepatocarcinogenesis in mice.

METHODSThe murine liver cancer cell strain Hepal-6 was transfected with IL-2 and/or B7-1 gene via recombinant adenovirus vectors and the liver cancer vaccines were prepared. C57BL/6 mice were immunized with the vaccines and challenged with the parental Hepal-6 cells afterwards. The immunoprotection was investigated and the reactive T cell line was assayed.

RESULTSThe effect of the Hep6-IL2/B7 vaccine on the onset of tumor formation was the strongest. The media survival time of the mice was the longest (68 days, P<0.05) and the implanted tumor was the smallest (P<0.05). The effect of single IL-2 or B7-1 gene-transfected vaccine was next to the co-transfected gene group with the mean survival time being 59 and 54 days, respectively. The mean survival time of wild or BGFP gene modified vaccine immunized group was 51 and 48 days, respectively. The control group all died within 38 days and the implanted tumor was the largest (P<0.05). The cellular immunofunction test and cytotoxicity study showed that the mice immunized with the Hep6-IL2/B7 vaccine gained significantly increased NK, LAK and CTL activity (29.0% +/- 2.5%, 65.0% +/- 2.9%, 83.1% +/- 1.5% respectively, compared with other groups P<0.05).

CONCLUSIONSThe IL-2 and B7-1 gene co-transfected liver cancer vaccines can induce the mice to produce activated and specific CTL against the parental tumor cells, and demonstrate stronger effect on the hepatocarcinogenesis than single gene modified or the regular tumor vaccine. Therefore, the vaccines may become a novel potential therapy for recurrence and metastases of HCC.

Adenoviridae ; genetics ; Animals ; B7-1 Antigen ; genetics ; immunology ; Cancer Vaccines ; administration & dosage ; genetics ; immunology ; Cell Division ; immunology ; Female ; Genetic Vectors ; administration & dosage ; genetics ; immunology ; Humans ; Interleukin-2 ; genetics ; immunology ; Killer Cells, Lymphokine-Activated ; immunology ; Killer Cells, Natural ; immunology ; Liver Neoplasms, Experimental ; immunology ; pathology ; prevention & control ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Survival Analysis ; T-Lymphocytes, Cytotoxic ; immunology ; Time Factors ; Transfection ; Tumor Cells, Cultured

The clinical application of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of hepatocellular carcinoma (HCC) patients. With the widespread applica-tion of ICIs in HCC, the management of immune-related adverse events (irAE) gained more and more attention. However, the complicated disease characteristics and various combination therapies in HCC throw out challenges to irAE management. Therefore, the editorial board of the 'Chinese expert consensus on the management of immune-related adverse events of hepatocellular carcinoma treated with immune checkpoint inhibitors (2021 edition)' organizes multidisciplinary experts to discuss and formulate this consensus. The consensus focuses on issues related to HCC irAE manage-ment, and puts forward suggestions, in order to improve standardized and safety clinical medication, so as to maximize the benefits of immunotherapy for patients.