title: Identification of immunogenic MAGED4B peptides for vaccine development in oral cancer immunotherapy.
abstract: The ever-increasing number of tumor-associated antigens has provided a major stimulus for the development of therapeutic peptides vaccines. Tumor-associated peptides can induce high immune response rates and have been developed as vaccines for several types of solid tumors, and many are at various stages of clinical testing. MAGED4B, a melanoma antigen, is overexpressed in oral squamous cell carcinoma (OSCC) and this expression promotes proliferation and cell migration. In this study, we have identified 9 short peptides derived from MAGED4B protein that are restricted in binding to the HLA subtypes common in the Asian population (HLA-A2, A11, and A24). The peptides had good binding affinity with the MHC-Class I molecules and stimulated ex-vivo IFN-gamma and Granzyme-B production in blood samples from OSCC patients, suggesting that they are immunogenic. Further, T cells stimulated with peptide-pulsed dendritic cells showed enhanced T-cell cytotoxic activity against MAGED4B-overexpressing OSCC cell lines. In summary, we have identified MAGED4B peptides that induce anti-tumor immune responses advocating that they could be further developed as vaccine candidates for the treatment of OSCC.
authors.affiliation: a Oral Cancer Research Team; Cancer Research Initiatives Foundation (CARIF) ; Subang Jaya , Selangor , Malaysia.
authors.forename: Kue Peng
authors.initials: KP
authors.lastname: Lim
authors.forename: Nicole Ai Leng
authors.initials: NA
authors.lastname: Chun
authors.forename: Chai Phei
authors.initials: CP
authors.lastname: Gan
authors.forename: Soo-Hwang
authors.initials: SH
authors.lastname: Teo
authors.forename: Zainal Ariff Abdul
authors.initials: ZA
authors.lastname: Rahman
authors.forename: Mannil Thomas
authors.initials: MT
authors.lastname: Abraham
authors.forename: Rosnah Binti
authors.initials: RB
authors.lastname: Zain
authors.forename: Sathibalan
authors.initials: S
authors.lastname: Ponniah
authors.forename: Sok Ching
authors.initials: SC
authors.lastname: Cheong
mesh_terms: D000328:Adult; D000951:Antigens, Neoplasm / Q000276:immunology*; D044466:Asian People; D019496:Cancer Vaccines / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D053804:Granzymes / Q000096:biosynthesis / Q000276:immunology; D059870:HLA-A11 Antigen / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D059871:HLA-A24 Antigen / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D059870:HLA-A11 Antigen; D015789:HLA-A2 Antigen; D059871:HLA-A24 Antigen; C430404:MAGE-E1 antigen, human; D007371:Interferon-gamma; D053804:Granzymes
keywords: APC, antigen presenting cell; DC, dendritic cell; HC, healthy control; HLA, human leukocyte antigen; MAGED4B; MAGED4B, melanoma-associated antigen D4B; MHC, major histocompatibility complex; OSCC, oral squamous cell carcinoma; PBMC, peripheral blood mononuclear cell; immune system; immunotherapy; oral cancer; peptide vaccine