This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Radkevich-Brown, O. Articles by Wei, W.-Z. Search for Related Content PubMed PubMed Citation Articles by Radkevich-Brown, O. Articles by Wei, W.-Z.

Genetic Regulation of the Response to Her-2 DNA Vaccination in Human Her-2 Transgenic Mice

¹ Karmanos Cancer Institute, Wayne State University, Detroit, Michigan and ² Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia

Requests for reprints: Wei-Zen Wei, Karmanos Cancer Institute, Wayne State University, 110 E. Warren Avenue, Detroit, Michigan, 48201. Phone: 313-578-4651; Fax: 313-578-4658; E-mail: weiw{at}karmanos.org.

Key Words: Her-2 • DNA vaccine • cancer vaccine • transgenic mice • regulatory T cell

Genetic regulation of immune reactivity to Her-2 vaccination and the consequent antitumor effect was tested in human Her-2 transgenic (Tg) mice of C57BL/6 (B6), BALB/c (BALB), and (B6x BALB) F1 (F1) background. Mice were electrovaccinated with Her-2 DNA with or without pretreatment with CD25 monoclonal antibody to remove CD25^hi regulatory T cells. When CD25⁺ T cells were intact, BALB Her-2 Tg mice were more responsive than the other two strains in both humoral and cellular immunities, and their tumor growth was significantly delayed. B6 Her-2 Tg mice responded poorly and F1 mice showed modest immune reactivity, but tumor growth did not change in either strain. Depletion of CD25^hi T cells before vaccination significantly improved protection from tumor challenge in F1 Her-2 Tg mice. This was associated with elevated levels of Her-2 IgG1, IgG2a, and IgG2c antibodies, and some mice also showed IFN- producing T-cell response. The same treatment induced modest improvement in B6 Her-2 Tg mice. In BALB Her-2 Tg mice, however, depletion of CD25^hi T cells did not further improve antitumor efficacy. Although their Her-2–specific IgG1 and interleukin-5–secreting T cells increased, the levels of IgG2a and IFN-–secreting T cells did not change. These results are the first to show genetic regulation of the response to a cancer vaccine and an unequal effect of removing CD25^hi T cells on antitumor immunity. These results warrant individualized treatment plans for patients with heterogeneous genetic backgrounds and possibly differential intrinsic immune reactivity to tumor antigens. [Cancer Res 2009;69(1):212–8]

This article has been cited by other articles:

				J. B. Jacob, Y.-c. M. Kong, I. Nalbantoglu, D. P. Snower, and W.-Z. Wei Tumor Regression following DNA Vaccination and Regulatory T Cell Depletion in neu Transgenic Mice Leads to an Increased Risk for Autoimmunity J. Immunol., May 1, 2009; 182(9): 5873 - 5881. [Abstract] [Full Text] [PDF]