Abstract 771: Therapy of spontaneous primary breast tumors in neu-N transgenic mice by adoptive transfer of vaccine-primed LN T cells also induces a humoral response

Abstract

Abstract To investigate factors which regulate T-cell mediated therapy of primary breast tumors in situ, we utilized neu-N transgenic mice. These neu-tolerant mice develop spontaneous breast tumors, several of which we have established as aggressive transplantable tumors and selected stem-like progenitor cells in vitro. We vaccinated neu-N mice with irradiated neupos breast cancer progenitor cells to prime T cells in draining LNs. We purified a minor subset (5% to 10%) of LN cells with a CD62Llow CD4+ or CD8+ phenotype representing recently activated effector cells. CD4 and CD8 subsets were separately activated in vitro with anti-CD3/IL-2/IL-7 for two stimulation cycles to induce 200-fold numerical expansion. Hosts bearing spontaneous primary breast tumors average 80 mm2 were treated with 35 × 106 of each CD4+ and CD8+ subsets. Even though the neu-tolerant hosts did not receive lymphodepletion prior to T cell transfer, the T cells significantly delayed tumor growth compared with untreated control mice (n=4 per group, p=0.037). This extends our previous work showing effective T cell therapy of inoculated lung metastases to primary in situ neu-N breast tumors. Neu is a transmembrane tumor antigen with shared expression between vaccine cells and spontaneous tumors that could contribute to the anti-tumor response. We also searched for evidence of response against other cross-reactive antigens. Interestingly, treated mice developed a humoral response and post-treatment serum IgG bound to neuneg variant tumor cells as well as neupos cell lines whereas pre-treatment serum was non-reactive. The development of an IgG serologic response following effective T cell-mediated therapy (in the absence of co-transferred B cells) indicates that transferred CD4+ T cells provided cognate helper function and immunoglobulin class switch signals to B cells and reversed tolerance to neu as well as other shared tumor antigens. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 771. doi:10.1158/1538-7445.AM2011-771