Ex Vivo Expansion of HER2-Specific T Cells for the Treatment of HER2-Overexpressing Breast Cancer
Annual summary rept. 3 Apr 2000-2 Apr 2003
WASHINGTON UNIV SEATTLE
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Adoptive T cell therapy has the potential to eradicate existing malignancy in humans. I have been investigating the efficacy of adoptive T cell therapy at eradicating malignancy in the neu-transgenic mouse model of human breast cancer. Helper peptides of neu have been identified to which T helper cell lines can be generated. Cell lines derived using these peptides, were tested for the ability to eradicate existing bulky malignancy. T cell injection resulted in a partial tumor response. I have been investigating how to improve efficacy. Polyclonal T cell lines recognizing multiple epitopes are more effective. I have observed that immunosuppressive T cells associate with these breast tumors. Prior elimination of these cells nay improve outcome. A monoclonal antibody therapy strategy has also been developed that will be tested in combination with adoptive T cell transfer. This is an adaptation of this murine model to better reflect current strategies in humans i.e. Herceptin Techniques for optimal ex vivo expansion of human HER-2neu-specific T cells are also continuing to be developed. Antigen-specificity of cultures can be preserved following rapid expansion with anti-CD3CD28 beads. The findings in the animal model and ex vivo expansion of human T cells will be directly translated to human clinical trials of adoptive T cell therapy.
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