Her-2/neu peptide vaccine induces antibodies with anti-tumor activity

Peptide vaccines derived from the extracellular domain of the tumor antigen Her-2/neu induce antibodies with anti-tumor activity in animal models, according to a report in the December 2003 International Journal of Cancer.

Her-2/neu is overexpressed in 20% to 30% of primary breast and prostate cancers, the authors explain, leading many investigators to develop vaccine strategies targeting the antigen.Dr. Ursula Wiedermann from University of Vienna, Austria and colleagues attempted to induce anti-Her-2/neu antibodies by peptide vaccination of mice and rabbits. They also sought to test the antibodies’ efficacy in inhibiting tumor cell growth in vitro.”The goal is to develop a prophylactic vaccine to be used for patients at risk,” Dr. Wiedermann told Reuters Health. “Alternatively, such a vaccine could be used in combination with chemotherapy, in order to prevent metastasis.”Sera from mice immunized with peptide P4 (amino acids 378-398) or peptide P7 (amino acids 610-623) or with the combination of peptides P6 (amino acids 544-560) and P7 induced significant Her-2/neu specific IgG, the authors report.These antibodies inhibited SK-BR-3 breast tumor cell proliferation by 16% (P4) and 9% (P6+P7), the report indicates, compared with 47% inhibition by the anti-Her-2/neu monoclonal antibody trastuzumab.The antibodies also mediated specific complement dependent lysis of SK-BR-3 cells at levels comparable to that of trastuzumab, the researchers note.Sera from rabbits immunized with a P4-P6-P7 mixture produced antibody-dependent cell-mediated cytotoxicity (ADCC) ranging from 31% to 46% cell lysis. In contrast, mouse sera failed to produce ADCC in SK-BR-3 cells, the investigators report, “probably due to an Fc-FcR mismatch of murine antibodies and human effector cells.”Mice that received 11 immunizations in 21-day intervals showed no histopathological signs of organ inflammation or toxicity, the results indicate.”We are very positive that specific prophylaxis based on the development of anti-tumor antibodies is a successful concept for tumor therapy and prevention,” Dr. Wiedermann said. “Moreover, changes from the systemic to the mucosal route of vaccine application might even enhance the patients’ compliance to undergo tumor immunotherapy.”Dr. Wiedermann added that studies of the coadministration of peptide vaccine with the putative T-helper 1-promoting cytokine IL-12 are underway in transgenic mice, with results expected during 2004.(Source: Int J Cancer 2003;107;976-983: Reuters Health: Will Boggs, MD: January 1, 2004: Oncolink)