Nonredundant roles of antibody, cytokines, and perforin in the eradication of established Her-2/neu carcinomas

Claudia Curcio, Emma Di Carlo, Raphael Clynes, Mark J. Smyth, Katia Boggio, Elena Quaglino, Michela Spadaro, Mario P. Colombo, Augusto Amici, Pier Luigi Lollini, Piero Musiani, Guido Forni

Research output: Contribution to journalArticle

Abstract

Since the mechanisms by which specific immunity destroys Her-2/neu carcinoma cells are highly undetermined, these were assessed in BALB/c mice vaccinated with plasmids encoding extracellular and transmembrane domains of the protein product (p185neu) of the rat Her-2/neu oncogene shot into the skin by gene gun. Vaccinated mice rejected a lethal challenge of TUBO carcinoma cells expressing p185neu. Depletion of CD4 T cells during immunization abolished the protection, while depletion of CD8 cells during the effector phase halved it, and depletion of polymorphonuclear granulocytes abolished all protection. By contrast, Ig μ-chain gene KO mice, as well as Fcγ receptor I/III, β-2 microglobulin, CD1, monocyte chemoattractant protein 1 (MCP1), IFN-γ, and perforin gene KO mice were protected. Only mice with both IFN-γ and perforin gene KOs were not protected. Although immunization also cured all BALB/c mice bearing established TUBO carcinomas, it did not cure any of the perforin KO or perforin and IFN-γ KO mice. Few mice were cured that had knockouts of the gene for Ig μ-chain, Fcγ receptor I/III, IFN-γ, or β-2 microglobulin. Moreover, vaccination cured half of the CD1 and the majority of the MCP1 KO mice. The eradication of established p185neu carcinomas involves distinct mechanisms, each endowed with a different curative potential.

Original languageEnglish
Pages (from-to)1161-1170
Number of pages10
JournalJournal of Clinical Investigation
Volume111
Issue number8
DOIs
Publication statusPublished - Apr 2003

ASJC Scopus subject areas

  • Medicine(all)

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    Curcio, C., Di Carlo, E., Clynes, R., Smyth, M. J., Boggio, K., Quaglino, E., Spadaro, M., Colombo, M. P., Amici, A., Lollini, P. L., Musiani, P., & Forni, G. (2003). Nonredundant roles of antibody, cytokines, and perforin in the eradication of established Her-2/neu carcinomas. Journal of Clinical Investigation, 111(8), 1161-1170. https://doi.org/10.1172/JCI200317426