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Nonredundant roles of antibody, cytokines, and perforin in the eradication of established Her-2/neu carcinomas
Claudia Curcio, … , Piero Musiani, Guido Forni
Claudia Curcio, … , Piero Musiani, Guido Forni
Published April 15, 2003
Citation Information: J Clin Invest. 2003;111(8):1161-1170. https://doi.org/10.1172/JCI17426.
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Article Vaccines

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

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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.

Authors

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

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Figure 1

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Cytotoxic and antibody response to p185neu of WT BALB/c mice shot at 2 w...
Cytotoxic and antibody response to p185neu of WT BALB/c mice shot at 2 week intervals with p185 plasmids. Spleens and sera were collected 2 weeks after the last immunization. The upper panel shows cytotoxicity of splenocytes evaluated in a 48-hour [3H]thymidine release assay against TUBO (squares, H-2d, p185neu positive), F1F-neu (triangles, H-2d, p185neu positive), N202.1A (filled circles, H-2q, p185neu positive); and F1F (open circles, H-2d, p185neu negative) targets. No significant cytotoxicity was found in mice shot with empty plasmids (data not shown). The lower panel shows the specific binding potential titer of anti-p185neu Ab in a pool of sera from WT BALB/c, BALB-IFNγKO, and BALB-μIgKO mice shot with empty (white bars) or p185 (black bars) plasmids.

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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