1.IL-12 Synergizes B7-1 Enhance the Antitumor Immunity in Experimental Mice
Zhihua WANG ; Xixiong KANG ; Tani KENZABURO ; Sumimoto HIDETOSHI ; Nakazaki YAKON ; Asano SHIGETAKA
Chinese Journal of Cancer Biotherapy 1994;0(01):-
Objective: To study the vaccine potency of gene-modified tumor cells, we have constructed IL-12, H7-1 and GM-CSF express vector using retrovirus. Methods: It was transfected into EL-4 thymic lylmphoma cells respectively and the effect of gene transduction on anti-tumor immunity were investigated. Results: The tumorigenicity of EL-4/IL-12 transfectant in C57BI/6 syn- ergistical mice was decreased significantly after implanted with EL-4/IL-12 transfectant compaired with EL-4/Wt or EL-4/Neo groups (P
2.Effect of Tumor Vaccine of EL-4 Cell Transduced with IL-12 Gene in C57BL/6 Mice
Zhihua WANG ; Xixiong KANG ; Kenzaburo TANI ; Hidetoshi SUMIMOTO ; Yukoh NAKAZAKA ; Shigetaka ASANO
Journal of Experimental Hematology 2000;8(2):118-121
In order to study the vaccine potency of gene-modified tumor cells, IL-12 express vector was constructed by using retrovirus. The vector was transfected into EL-4 thymic lymphoma cells and the effect of transfectant on anti-tumor immunity was investigated. The tumorigenicity of EL-4/IL-12 transfectant in syngeneic C57BL/6 mice was decreased significantly after implanted with EL-4/IL-12 transfectant compared with EL-4/Wt or EL-4/Neo groups (P < 0.001). The systemic protective immunity was induced against the challenge with EL-4/Wt (in 8/10 mice) after the rejection of EL-4/IL-12 in vivo experiment, a stronger CTL activity against EL-4/Wt cells and a weak killer activity against syngeneic Lewis lung carcinoma (LLC) cells were obtained in (51)Cr release assay. In vivo depletion analysis suggested that the decreased tumorigenicity mainly depended on CD4(+), CD8(+) and NK cells. Therapeutic vaccines with EL-4/IL-12 cells could retard the growth of established EL-4/Wt tumors significantly compared with those of EL-4/Neo (P < 0.005). These studies suggested that immunotherapy and gene therapy using IL-12 is effective in hematopoietic malignancy and IL-12 has prospects of application in human cancer treatment in the near future.