IgG2a induced by interleukin (IL) 12-producing tumor cell vaccines but not IgG1 induced by IL-4 vaccine is associated with the eradication of experimental metastases.
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) alpha. Irradiated IL-12- and IL-4-producing C26/FR alpha cell vaccines cured 50 and 30% of mice bearing C26/FR alpha 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-FR alpha 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-FR alpha 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.
Rodolfo
M
M
Experimental Oncology D, Istituto Nazionale Tumori, Milan, Italy. rodolfo@istitutotumori.mi.it
Melani
C
C
Zilocchi
C
C
Cappetti
B
B
Luison
E
E
Arioli
I
I
Parenza
M
M
Canevari
S
S
Colombo
M P
MP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000912:Antibodies, Neoplasm / Q000096:biosynthesis; D019496:Cancer Vaccines; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D014611:Vaccination
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D007074:Immunoglobulin G; D018664:Interleukin-12; D015847:Interleukin-4