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

Monica Rodolfo, Cecilia Melani, Chiara Zilocchi, Barbara Cappetti, Elena Luison, Ivano Arioli, Mariella Parenza, Silvana Canevari, Mario P. Colombo

Research output: Contribution to journalArticlepeer-review

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) 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.

Original languageEnglish
Pages (from-to)5812-5817
Number of pages6
JournalCancer Research
Volume58
Issue number24
Publication statusPublished - Dec 15 1998

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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