We evaluated whether antibody response correlates with tumor therapy by cytokine gene-modified tumor cell vaccines. To characterize the antibody (Ab) response against a known antigen, colon carcinoma C26 cells and C26 variants engineered to produce interleukin (IL) 12 or IL-4 were further transduced to express the human tumor-associated antigen gp38 folate receptor (FR) α. Irradiated IL-12- and IL-4-producing C26/FRα cell vaccines cured 50 and 30% of mice bearing C26/FRα lung micrometastases. Treatment induced a rapid, CD4-dependent Ab production dominated by IgG2a and IgG1 in response to the IL-12 or IL-4 vaccine, respectively. In contrast, untreated tumor-bearing mice showed a late serological response dominated by IgM. Anti-FRα IgG1 and IgG2a were able to suppress tumor metastases upon passive transfer in vivo. Sera from mice cured by the IL-12 vaccine displayed a higher binding activity, a higher anti-FRα IgG2a content, and a higher complement-mediated tumor cell lysis in vitro compared to the sera from nonresponder mice. Such a correlation was not found in the sera of mice treated with the IL-4 vaccine. These data indicate that cytokine-producing tumor cell vaccines strongly influence antibody response, and that in the case of the IL-12-based vaccine, the Ab titer correlates with the therapeutic response, thus suggesting its use for monitoring the outcome of vaccination in cancer patients.
Supported by the Italian Association for Cancer Research, the Istituto Superiore di Sanità Special Program on Gene Therapy, and the Consiglio Nazionale delle Ricerche.