PMID- 12697735 OWN - NLM STAT- MEDLINE DCOM- 20030508 LR - 20201215 IS - 0021-9738 (Print) IS - 0021-9738 (Linking) VI - 111 IP - 8 DP - 2003 Apr TI - Nonredundant roles of antibody, cytokines, and perforin in the eradication of established Her-2/neu carcinomas. PG - 1161-70 AB - 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 (p185(neu)) 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 p185(neu). 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 mu-chain gene KO mice, as well as Fcgamma receptor I/III, beta-2 microglobulin, CD1, monocyte chemoattractant protein 1 (MCP1), IFN-gamma, and perforin gene KO mice were protected. Only mice with both IFN-gamma 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-gamma KO mice. Few mice were cured that had knockouts of the gene for Ig mu-chain, Fcgamma receptor I/III, IFN-gamma, or beta-2 microglobulin. Moreover, vaccination cured half of the CD1 and the majority of the MCP1 KO mice. The eradication of established p185(neu) carcinomas involves distinct mechanisms, each endowed with a different curative potential. FAU - Curcio, Claudia AU - Curcio C AD - Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy. FAU - Di Carlo, Emma AU - Di Carlo E FAU - Clynes, Raphael AU - Clynes R FAU - Smyth, Mark J AU - Smyth MJ FAU - Boggio, Katia AU - Boggio K FAU - Quaglino, Elena AU - Quaglino E FAU - Spadaro, Michela AU - Spadaro M FAU - Colombo, Mario P AU - Colombo MP FAU - Amici, Augusto AU - Amici A FAU - Lollini, Pier-Luigi AU - Lollini PL FAU - Musiani, Piero AU - Musiani P FAU - Forni, Guido AU - Forni G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Clin Invest JT - The Journal of clinical investigation JID - 7802877 RN - 0 (Antibodies, Neoplasm) RN - 0 (Cancer Vaccines) RN - 0 (Cytokines) RN - 0 (Membrane Glycoproteins) RN - 0 (Pore Forming Cytotoxic Proteins) RN - 0 (Vaccines, DNA) RN - 126465-35-8 (Perforin) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM CIN - J Clin Invest. 2003 Apr;111(8):1116-8. PMID: 12697728 MH - Animals MH - Antibodies, Neoplasm/*physiology MH - Biolistics MH - Cancer Vaccines/*immunology MH - Cytokines/*physiology MH - Female MH - Graft Rejection MH - Membrane Glycoproteins/*physiology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Knockout MH - Neoplasm Transplantation MH - Neoplasms, Experimental/*therapy MH - Perforin MH - Pore Forming Cytotoxic Proteins MH - Receptor, ErbB-2/*immunology MH - Vaccination MH - Vaccines, DNA/*immunology PMC - PMC152940 EDAT- 2003/04/17 05:00 MHDA- 2003/05/09 05:00 PMCR- 2003/04/15 CRDT- 2003/04/17 05:00 PHST- 2003/04/17 05:00 [pubmed] PHST- 2003/05/09 05:00 [medline] PHST- 2003/04/17 05:00 [entrez] PHST- 2003/04/15 00:00 [pmc-release] AID - 17426 [pii] AID - 10.1172/JCI17426 [doi] PST - ppublish SO - J Clin Invest. 2003 Apr;111(8):1161-70. doi: 10.1172/JCI17426.