Induction of Both CD8+ and CD4+ T-Cell–Mediated Responses in Colorectal Cancer Patients by Colon Antigen-1

Purpose: Colon antigen-1 (COA-1) was recently identified as a novel antigen of colorectal cancer encoded by the UBXD5 gene. Here, we evaluated whether a specific T-cell-mediated response directed against this molecule can occur in colorectal cancer patients. Experimental Design: Antigen- and tumor-specific immunologic responses of peripheral blood mononuclear cells (PBMC) stimulated in vitro with the MHC class II-associated immunogenic epitope of COA-1 (FSTFPPTLYQDDTLTLQAAG) were analyzed by IFN-γ ELISPOT assay. Results: COA-1-specific and tumor-reactive T lymphocytes were isolated from all ( n = 7) HLA-DRβ1*0402 + or *1301 + colorectal cancer patients with progressive disease (Dukes9 C and D) but not in patients ( n = 4) with early-stage tumor (Dukes9 A and B) and in healthy donors ( n = 5), suggesting that the immune response against this antigen is associated with the progression of colorectal cancer. COA-1- and tumor-specific T lymphocytes displayed a CD3 + CD4 + CD69 + CD45RA + phenotype, compatible with the activated effector-type T-cell subset, and most of them exerted cytotoxic activity against HLA-matched and COA-1 + tumor cells. COA-1-specific T cells could also be isolated by in vitro stimulation of peripheral blood mononuclear cells with autologous dendritic cells loaded with tumor lysate, suggesting that this antigen can generate a dominant immunologic response against colorectal cancer cells. Notably, we could identify also COA-1-derived epitopes binding to HLA-A*0201 molecules that elicited antigen- and tumor-specific CD8 + T-cell-mediated responses in colorectal cancer patients. Conclusions: Both CD4 + and CD8 + T-cell responses against COA-1 can occur in colorectal cancer patients with metastatic disease, suggesting that this antigen is suitable for immunotherapeutic protocols of these patients.