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.

Abstract:

: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.

journal_name

Cancer Res

journal_title

Cancer research

authors

Rodolfo M,Melani C,Zilocchi C,Cappetti B,Luison E,Arioli I,Parenza M,Canevari S,Colombo MP

subject

Has Abstract

pub_date

1998-12-15 00:00:00

pages

5812-7

issue

24

eissn

0008-5472

issn

1538-7445

journal_volume

58

pub_type

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