PMID- 14624313 OWN - NLM STAT- MEDLINE DCOM- 20040519 LR - 20240427 IS - 0340-7004 (Print) IS - 1432-0851 (Electronic) IS - 0340-7004 (Linking) VI - 53 IP - 5 DP - 2004 May TI - Identification of a MHC class-II restricted epitope in carcinoembryonic antigen. PG - 391-403 AB - PURPOSE: The carcinoembryonic antigen (CEA) is extensively expressed on the vast majority of colorectal, gastric, and pancreatic carcinomas, and, therefore, is a good target for tumor immunotherapy. CD4+ T-helper (Th) cells play a critical role in initiation, regulation, and maintenance of immune responses. In this study, we sought to identify Th epitopes derived from CEA which can induce CEA-specific Th responses. The combined application with cytotoxic T lymphocyte (CTL) epitopes would be more potent than tumor vaccines that primarily activate CTL alone. METHODS: We utilized a combined approach of using a computer-based algorithm analysis TEPITOPE and in vitro biological analysis to identify Th epitopes in CEA. RESULTS: Initial screening of healthy donors showed that all five predicted peptides derived from CEA could induce peptide-specific T-cell proliferation in vitro. We characterized these CEA epitopes by establishing and analyzing peptide-specific T-cell clones. It was shown that CD4+ T-cells specific for the CEA(116 )epitope can recognize and respond to naturally processed CEA protein and CEA(116 )epitope can be promiscuously presented by commonly found major histocompatibility complex (MHC) alleles. Furthermore, it was demonstrated that immunization of human leukocyte antigen (HLA)-DR4 transgenic mice with CEA(116) peptide elicited antigen-specific Th responses which can recognize the antigenic peptides derived from CEA protein and CEA-positive tumors. CONCLUSION: The MHC class II-restricted epitope CEA(116) could be used in the design of peptide-based tumor vaccine against several common cancers expressing CEA. FAU - Shen, Lei AU - Shen L AD - Center for Cell and Gene Therapy, Baylor College of Medicine, One Baylor Plaza, Alkek Bldg. N1004, Houston, TX 77030, USA. FAU - Schroers, Roland AU - Schroers R FAU - Hammer, Juergen AU - Hammer J FAU - Huang, Xue F AU - Huang XF FAU - Chen, Si-Yi AU - Chen SY LA - eng GR - R01 AI048711/AI/NIAID NIH HHS/United States GR - AI48711/AI/NIAID NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. DEP - 20031118 PL - Germany TA - Cancer Immunol Immunother JT - Cancer immunology, immunotherapy : CII JID - 8605732 RN - 0 (Carcinoembryonic Antigen) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA-DR4 Antigen) RN - 0 (Peptide Fragments) RN - 82115-62-6 (Interferon-gamma) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) SB - IM MH - Algorithms MH - Animals MH - Antigen Presentation/immunology MH - Carcinoembryonic Antigen/*immunology MH - Cell Division MH - Dendritic Cells/immunology MH - Enzyme-Linked Immunosorbent Assay MH - Epitope Mapping MH - Epitopes, T-Lymphocyte/genetics/*immunology MH - Genes, MHC Class II/*immunology MH - Granulocyte-Macrophage Colony-Stimulating Factor/immunology/metabolism MH - HLA-DR4 Antigen/genetics/*immunology MH - Humans MH - Immunization MH - Interferon-gamma/metabolism MH - Mice MH - Mice, Transgenic MH - Peptide Fragments/*immunology MH - T-Lymphocytes, Cytotoxic/immunology MH - T-Lymphocytes, Helper-Inducer/*immunology MH - Tumor Cells, Cultured PMC - PMC11034193 EDAT- 2003/11/19 05:00 MHDA- 2004/05/20 05:00 PMCR- 2003/11/18 CRDT- 2003/11/19 05:00 PHST- 2003/06/09 00:00 [received] PHST- 2003/09/03 00:00 [accepted] PHST- 2003/11/19 05:00 [pubmed] PHST- 2004/05/20 05:00 [medline] PHST- 2003/11/19 05:00 [entrez] PHST- 2003/11/18 00:00 [pmc-release] AID - 455 [pii] AID - 10.1007/s00262-003-0455-y [doi] PST - ppublish SO - Cancer Immunol Immunother. 2004 May;53(5):391-403. doi: 10.1007/s00262-003-0455-y. Epub 2003 Nov 18.