Carcinoembryonic antigen (CEA) is a potential target for
antigen-specific
immunotherapy, as it is frequently overexpressed in human
carcinomas. Moreover, an
epitope derived from CEA, designated
CAP1 (YLSGANLNL), has been proposed as naturally processed and presented by
tumors in the
human leukocyte antigen (
HLA)-A*0201 context. Our aim was to fully characterize and assess the clinical relevance of the
HLA-A*0201-restricted cytotoxic T lymphocyte (CTL) response against CEA. Stable and potent artificial antigen presenting cells (AAPCs) were used to evaluate T-cell response against CEA. These cells efficiently activate CTLs against
tumor-derived
epitopes after transduction with the antigenic
peptides or full-length
proteins. We found that AAPCs genetically modified to express
CAP1, the agonist
peptide CAP1-6D, or the whole CEA
protein were not able to activate CAP1-specific CTLs from
HLA-A*0201+ healthy donors or patients with
colorectal carcinoma, even after multiple stimulations. In addition, we showed that a CAP1-specific T-cell clone, obtained after multiple stimulations of T cells of a
HLA-A*0201+ healthy donor in vitro with
autologous antigen presenting cells, recognized CEA(-)
HLA-A*0201+
tumors transduced with a minigene encoding
CAP1 but failed to react against
HLA-A*0201+
tumor cells expressing CEA. Finally, AAPCs expressing the whole CEA
protein did not induce any specific CTL response against CEA+
HLA-A*0201+
tumor cells highlighting the potential difficulty of mounting an efficacious T-cell response against this
autoantigen. Altogether, our data indicate that
CAP1 is not efficiently processed and presented by CEA+
tumor cells, and therefore, is not an appropriate target for T-cell-based
immunotherapy.