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
Abstract
We initially identified and characterized a CD2-mediated, interleukin (IL)-12-dependent signaling pathway which inhibits apoptosis in mitogen-stimulated human gamma delta-T cells. We have since exploited this pathway to develop the methodologies allowing the large-scale ex vivo expansion of viable apoptosis-resistant gamma delta-T cells-- an undertaking until now, not possible. Importantly, we have shown that apoptosis-resistant human gamma delta-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 gamma delta-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 year of this award. Although the human pre-clinical work is too preliminary to report at this point, we have made some important progressin optimizing our animal models to assess the ability of gamma delta-T cells to moderate tumor growth in a syngeneic model of breast cancer. Problems encountered in the first year-- and their solutions--are discussed in this first annual report.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2007
- Accession Number
- ADA520719
Entities
People
- Richard D. Lopez
Organizations
- University of Alabama