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

摘要

During the last research year, we have made progress in two main areas. First, we have shown that neu-specific T cells can significantly inhibit growth of spontaneous mammary tumors; we plan to conduct T cell infusion studies in the spontaneous tumor model whenever possible. Second, we have made advances in understanding how and why the ex vivo cytokine environment in which the T cells are cultured impacts their clinical efficacy. We had hypothesized that the ex vivo cytokine milieu in which antigen-specific T cells are expanded in can greatly influence their function and clinical activity in vivo. We found that by simply adding IL-21 to IL-2 in culture, or by depleting IL-10 in the culture, we induced significant changes to the cytokine profile of those cultured T cells, which in turn enhanced their antitumor efficacy. IL-21 may enhance efficacy via induction of two proinflammatory cytokines, IL-17 and TNF- a. Anti-IL-10 antibody may enhance the clinical efficacy of the T cells via the inhibition of IL-10 production. For all 9 T cell culture conditions tested, there was uniformly high induction of IL-5, IL-6, IL-10, IL-13, IFN-g, TNF-a and GM-CSF, and low induction of IL-7, IL-12, IL-15 and IL-2. Overall, we discovered that the choice of culture cytokines in which T cells are grown for adoptive transfer studies is critical.