IMMUNOTHERAPY OF EXPERIMENTAL METASTASES BY VACCINATION WITH INTERLEUKIN GENE-TRANSDUCED ADENOCARCINOMA CELLS SHARING TUMOR-ASSOCIATED ANTIGENS - COMPARISON BETWEEN IL-12 AND IL-2 GENE-TRANSDUCED TUMOR-CELL VACCINES

We have compared the therapeutic activity and characterized the antitu mor response induced by IL-12 and IL-2 gene-transduced tumor cell vacc ines, Mice bearing lung metastases of the BALB/c colon carcinoma C51 w ere treated with syngenic, histologically related, and antigenically c ross-reacting irradiated IL-12 (C26/IL12) or IL-2 (C26/IL2) gene-trans duced C26 tumor cells given s.c. Vaccination with C26/IL12 cells cured 30% of mice, while vaccination with C26/IL2 cells reduced the number of metastatic nodules without affecting survival, Despite this differe nce, similar antitumor CTL activation was shown in mice treated with C 26/IL12 or C26/IL2 cells, The lytic pattern of CTL was shown to be dir ected to tumor-associated Ags (TAA) shared between the colon carcinoma s C51, C26, and CC36 as well as with other syngenic tumors, Both treat ments induced anti-TAA Abs, but only sera from mice treated with C26/I L12 contained Ab that lysed tumor cells in a C-dependent cytotoxicity assay, Early infiltration of activated T cells was found in the lungs of mice vaccinated with C26/IL12, CD4(+) lymphocytes purified from the lymph nodes draining the vaccination site or from the spleen showed a higher production of IFN-gamma in response to anti-CDS mAb in C26/IL1 2 vaccinated mice, while a higher production of IL-4 was shown in mice vaccinated with C26/IL2 cells, These results indicate that the better therapeutic efficacy of vaccination with C26/IL12 is associated with the production of C-binding Ab, an early infiltration of the metastati c lungs by activated T lymphocytes and a predominant systemic activati on of Th1 more than Th2 cells.