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Enhancing the Breadth of Efficacy of Therapeutic Vaccines for Breast Cancer

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Technical Report,25 Sep 2014,24 Sep 2015

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University of Colorado School of Medicine Aurora United States

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The major objective of this project, in collaboration with the other teams at Oregon Health and Science University and City of Hope, is to develop novel strategies to enhance the protective effects of anti-tumor T cells in breast cancer bc patients based on the hypothesis that partially protective anti-tumor T cells exist within in most bc patients. We previously determined that the sequence of the TCR of T cell clones expanded in culture must be compared with those isolated ex vivo because their TCR repertoires are skewed in culture. Since the T cells cannot be cultured, we developed an emulsion PCR assay to sequence the alpha and beta chain of single T cells in one reaction. Using this assay we identified TCRs enriched in tumor infiltrating lymphocytes, and found at low levels in the peripheral blood. A panel of TCRs were found in multiple patients suggesting that targeting these TCRs maybe most efficient and that they are restricted by the HLA-A2 molecule, the HLA that the bc patients all have in common. With this technique in hand, we are positioned to screen known bc antigens and peptideMHC libraries for new bc epitopes and mimotopes.

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