Use of two predictive algorithms of the world wide web for the identification of tumor-reactive T-cell epitopes.
Tumor cells can be effectively recognized and eliminated by CTLs. One approach for the development of CTL-based cancer immunotherapy for solid tumors requires the use of the appropriate immunogenic peptide epitopes that are derived from defined tumor-associated antigens. Because CTL peptide epitopes are restricted to specific MHC alleles, to design immune therapies for the general population it is necessary to identify epitopes for the most commonly found human MHC alleles. The identification of such epitopes has been based on MHC-peptide-binding assays that are costly and labor-intensive. We report here the use of two computer-based prediction algorithms, which are readily available in the public domain (Internet), to identify HL4-B7-restricted CTL epitopes for carcinoembryonic antigen (CEA). These algorithms identified three candidate peptides that we studied for their capacity to induce CTL responses in vitro using lymphocytes from HLA-B7+ normal blood donors. The results show that one of these peptides, CEA9(632) (IPQQHTQVL) was efficient in the induction of primary CTL responses when dendritic cells were used as antigen-presenting cells. These CTLs were efficient in killing tumor cells that express HLA-B7 and produce CEA. The identification of this HLA-B7-restricted CTL epitope will be useful for the design of ethnically unbiased, widely applicable immunotherapies for common solid epithelial tumors expressing CEA. Moreover, our strategy of identifying MHC class I-restricted CTL epitopes without the need of peptide/HLA-binding assays provides a convenient and cost-saving alternative approach to previous methods.
Lu
J
J
Department of Immunology and Cancer Center, Mayo Clinic and Mayo Graduate School, Rochester, Minnesota 55905, USA.
Celis
E
E
D000465:Algorithms; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D017951:Antigen Presentation / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000276:immunology* / Q000378:metabolism; D002461:Cell Line, Transformed; D003713:Dendritic Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015793:HLA-B7 Antigen / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016219:Immunotherapy, Adoptive; D020407:Internet; D008213:Lymphocyte Activation / Q000276:immunology; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D011237:Predictive Value of Tests; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D018984:Epitopes, T-Lymphocyte; D015793:HLA-B7 Antigen; D010446:Peptide Fragments