title: Identification of a broad coverage HLA-DR degenerate epitope pool derived from carcinoembryonic antigen.
abstract: CD4 T cells are important for anti-tumor immune responses. Aside from their role in the activation of CD8 T cells, CD4 T cells also mediate anti-tumor immune responses by recruiting innate immune effectors into the tumor microenvironment. Thus, the search for strategies to boost CD4 T cell immunity is an active area of research. Our goal in this study was to identify HLA-DR epitopes of carcinoembryonic antigen (CEA), a commonly over-expressed tumor antigen. HLA-DR epitopes of CEA were identified using the epitope prediction program, PIC (predicted IC(50)) and tested using in vitro HLA-DR binding assays. Following CEA epitope confirmation, IFN-gamma ELIspot assays were used to detect existing immunity against the HLA-DR epitope panel of CEA in breast and ovarian cancer patients. In vitro generated peptide-specific CD4 T cells were used to determine whether the epitopes are naturally processed from CEA protein. Forty-three epitopes of CEA were predicted, 15 of which had high binding affinity for 8 or more common HLA-DR molecules. A degenerate pool of four, HLA-DR restricted 15 amino acid epitopes (CEA.24, CEA.176/354, CEA.488, and CEA.653) consisting of two novel epitopes (CEA.24 and CEA.488) was identified against which 40% of breast and ovarian cancer patients had pre-existent T cell immunity. All four epitopes are naturally processed by antigen-presenting cells. Hardy-Weinberg analysis showed that the pool is useful in approximately 94% of patients. Patients with breast or ovarian cancer demonstrate pre-existent immune responses to the tumor antigen CEA. The degenerate pool of CEA peptides may be useful for augmenting CD4 T cell immunity.
authors.affiliation: Department of Immunology, College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Lavakumar
authors.initials: L
authors.lastname: Karyampudi
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Krco
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Kalli
authors.forename: Courtney L
authors.initials: CL
authors.lastname: Erskine
authors.forename: Lynn C
authors.initials: LC
authors.lastname: Hartmann
authors.forename: Karin
authors.initials: K
authors.lastname: Goodman
authors.forename: James N
authors.initials: JN
authors.lastname: Ingle
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Maurer
authors.forename: Aziza
authors.initials: A
authors.lastname: Nassar
authors.forename: Chao
authors.initials: C
authors.lastname: Yu
authors.forename: Mary L
authors.initials: ML
authors.lastname: Disis
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Wettstein
authors.forename: John D
authors.initials: JD
authors.lastname: Fikes
authors.forename: Melanie
authors.initials: M
authors.lastname: Beebe
authors.forename: Glenn
authors.initials: G
authors.lastname: Ishioka
authors.forename: Keith L
authors.initials: KL
authors.lastname: Knutson
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D000939:Epitopes; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000276:immunology; D012984:Software
chemical_list: D002272:Carcinoembryonic Antigen; D000939:Epitopes; D006684:HLA-DR Antigens