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IL-12 Synergizes B7-1 Enhance the Antitumor Immunity in Experimental Mice
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Abstract:
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<0. 01). The systemic protective immunity was induced against the challenge with EL-4/Wt (in 10/15 mice) after the rejection of EL-4/IL-12 in the experiment, a stronger CTL activity against EL-4/Wt cells and a weak killer activity against syn- geneic Lewis Lung Carcinoma cells were obtained in 51Cr 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 to estabished EL-4/Wt tumors significantly compared with those of EL-4/Neo(P < 0 .005 ), combination of therapeutic vaccines of EL-4/IL-12 and EL-4/B7-1 result in the enhanced the therapeutic effect of each single transficants (P < 0 .005) in this experimental model. Conclution: These studies suggested that immunogene treatment using IL-12 is effective in hematopoi- etic malignancy, and combination of IL-12 with B7-1 have a aplication value in human cancer treatment in the near future.
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Clc Number:
R730.51
