title: Identification of Four-Jointed Box 1 (FJX1)-Specific Peptides for Immunotherapy of Nasopharyngeal Carcinoma.
abstract: Nasopharyngeal carcinoma (NPC) is highly prevalent in South East Asia and China. The poor outcome is due to late presentation, recurrence, distant metastasis and limited therapeutic options. For improved treatment outcome, immunotherapeutic approaches focusing on dendritic and autologous cytotoxic T-cell based therapies have been developed, but cost and infrastructure remain barriers for implementing these in low-resource settings. As our prior observations had found that four-jointed box 1 (FJX1), a tumor antigen, is overexpressed in NPCs, we investigated if short 9-20 amino acid sequence specific peptides matching to FJX1 requiring only intramuscular immunization to train host immune systems would be a better treatment option for this disease. Thus, we designed 8 FJX1-specific peptides and implemented an assay system to first, assess the binding of these peptides to HLA-A2 molecules on T2 cells. After, ELISPOT assays were used to determine the peptides immunogenicity and ability to induce potential cytotoxicity activity towards cancer cells. Also, T-cell proliferation assay was used to evaluate the potential of MHC class II peptides to stimulate the expansion of isolated T-cells. Our results demonstrate that these peptides are immunogenic and peptide stimulated T-cells were able to induce peptide-specific cytolytic activity specifically against FJX1-expressing cancer cells. In addition, we demonstrated that the MHC class II peptides were capable of inducing T-cell proliferation. Our results suggest that these peptides are capable of inducing specific cytotoxic cytokines secretion against FJX1-expressing cancer cells and serve as a potential vaccine-based therapy for NPC patients.
authors.affiliation: Cancer Research Initiatives Foundation (CARIF), Sime Darby Medical Centre, Subang Jaya, Selangor, Malaysia.
authors.forename: San Jiun
authors.initials: SJ
authors.lastname: Chai
authors.affiliation: Department of Surgery, Clinical Campus Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia.
authors.forename: Yoke Yeow
authors.initials: YY
authors.lastname: Yap
authors.affiliation: Department of Oncology, Sime Darby Medical Centre, Subang Jaya, Selangor, Malaysia.
authors.forename: Yoke Ching
authors.initials: YC
authors.lastname: Foo
authors.affiliation: Cancer Research Initiatives Foundation (CARIF), Sime Darby Medical Centre, Subang Jaya, Selangor, Malaysia.
authors.forename: Lee Fah
authors.initials: LF
authors.lastname: Yap
authors.affiliation: Department of Surgery, Cancer Vaccine Development Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.
authors.forename: Sathibalan
authors.initials: S
authors.lastname: Ponniah
authors.affiliation: Cancer Research Initiatives Foundation (CARIF), Sime Darby Medical Centre, Subang Jaya, Selangor, Malaysia.
authors.forename: Soo Hwang
authors.initials: SH
authors.lastname: Teo
authors.affiliation: Cancer Research Initiatives Foundation (CARIF), Sime Darby Medical Centre, Subang Jaya, Selangor, Malaysia.
authors.forename: Sok Ching
authors.initials: SC
authors.lastname: Cheong
authors.affiliation: Cancer Research Initiatives Foundation (CARIF), Sime Darby Medical Centre, Subang Jaya, Selangor, Malaysia.
authors.forename: Vyomesh
authors.initials: V
authors.lastname: Patel
authors.affiliation: Cancer Research Initiatives Foundation (CARIF), Sime Darby Medical Centre, Subang Jaya, Selangor, Malaysia.
authors.forename: Kue Peng
authors.initials: KP
authors.lastname: Lim
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D058501:Enzyme-Linked Immunospot Assay; D015789:HLA-A2 Antigen / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D011485:Protein Binding; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D016207:Cytokines; C000592900:FJX1 protein, human; D015789:HLA-A2 Antigen; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010455:Peptides; D007371:Interferon-gamma