Innate Anti-Breast Cancer Activity of (Gamma)/(Delta) T-Cells: A Novel Biological and Clinical Approach to the Treatment of Relapsed or Refractory Breast Cancer; Annual rept. 3 Feb 2007-2 Feb 2008

摘要

We initially identified and characterized a CD2-mediated interleukin (IL)-12-dependent signaling pathway which inhibits apoptosis in mitogen- stimulated human -T cells. We have since exploited this pathway to develop the methodologies allowing the large-scale ex vivo expansion of viable apoptosis- resistant -T cells - an undertaking until now not possible. Importantly we have shown that apoptosis- resistant human -T cells retain significant innate major histocompatibility complex (MHC)-unrestricted cytotoxicity against a wide variety of human-derived tumor cell lines including human breast cancer cell lines. Our efforts related to this proposal have remained focused upon testing the hypothesis that -T cells - by virtue of their innate ability to recognize and kill epithelial-derived malignancies - play an important role in regulating the initial growth or spread of breast cancer in vivo. In this progress report we discuss the findings we have made in the first and second years of this award. The human pre-clinical work is reported here as we have made some important progress in optimizing our ability to expand -T cells from patients with breast cancer. Data derived from animal studies using the syngeneic model of breast cancer are very preliminary but will be discussed briefly in this year's report. Problems encountered in the first two year - and their solutions - are discussed in this annual report.