Spontaneous T-cell responses against peptides derived from the Taxol resistance–associated gene-3 (TRAG-3) protein in cancer patients

摘要: Expression of the cancer-testis antigen Taxol resistance–associated gene-3 (TRAG-3) protein is associated with acquired paclitaxel (Taxol) resistance, and expressed in various cancer types; e.g., breast cancer, leukemia, melanoma. Thus, TRAG-3 represents an attractive target for immunotherapy cancer. To identify HLA-A*02.01–restricted epitopes from TRAG-3, we screened patients spontaneous cytotoxic T-cell responses against TRAG-3–derived peptides. The sequence was 9mer 10mer peptides possessing HLA-A*02.01–binding motifs. Of 12 potential binders, 9 were indeed capable binding to HLA-A*02.01 molecule, affinities ranging strong weak binders. Subsequently, lymphocytes (9 patients, melanoma 13 hematopoietic malignancies) analyzed reactivity panel by ELISpot assay. Spontaneous immune detected 8 epitope candidates 7 5 malignancies. In several cases, TRAG-3–specific CTL scattered over epitopes. Hence, no immunodominance any single peptide observed. Furthermore, single-peptide 2 healthy HLA-A2+ donors, but detectable HLA-A2− donors or 4 patients. identified are targets these represent structures future therapeutic vaccinations possibly appropriate strategies that combine vaccination chemotherapy; i.e., treatment.