CD4+ Th1 HER2-Specific T Cells as a Novel Treatment for HER2- Overexpressing Breast Cancer

摘要

During the last research period, we have made significant progress in the development of our mouse neu-reactive T cell lines. First, we have confirmed the key CD4+ neu peptides (p101 and p373) most effective at priming T cell responses. Of the peptide-specific T cell lines tested, only p101- and p373- T cells induced both peptide- and protein-specific responses. In preliminary studies involving adjuvants, GMCSF was highly effective for use with our peptide vaccines. Second, we have thoroughly characterized the cytokine production by our ex vivo expanded T cells and observed high levels of secreted Th1 cytokines, primarily IFN and GM-CSF, but also, interestingly, Th2 cytokines, primarily IL-5 and IL-6. Furthermore, IL-17, a pro-inflammatory cytokine, was also found to be secreted by the cultured T cells during ex vivo expansion. Our studies have also demonstrated that the addition of IL-7 (among all the tested cytokines) to IL-2 in the T cell culture regimen is necessary for optimal ex vivo growth. Third, we have clearly demonstrated that our neu specific T cell lines were highly effective at inhibiting tumor growth, particularly MP (multiple peptide)-specific T cells. Three T cell infusions were more effective at inducing tumor regression than a single infusion. Most importantly, the antitumor inhibition was mediated by endogenous CD8+ T cells.