title: Identification of DRG-1 As a Melanoma-Associated Antigen Recognized by CD4+ Th1 Cells.
abstract: Immunotherapy has emerged as a promising strategy for the treatment of metastatic melanoma. Clinical studies have demonstrated the feasibility of cancer immunotherapy using tumor antigens recognized by CD8(+) T cells. However, the overall immune responses induced by these antigens are too weak and transient to induce tumor regression in the majority of patients who received immunization. A growing body of evidence suggests that CD4(+) T helper (Th) cells play an important role in antitumor immunity. Therefore, the identification of MHC class II-restricted tumor antigens capable of stimulating CD4(+) T cells may provide opportunities for developing effective cancer vaccines. To this end, we describe the identification of developmentally regulated GTP-binding protein 1 (DRG-1) as a melanoma-associated antigen recognized by HLA-DR11-restricted CD4(+) Th1 cells. Epitope mapping analysis showed that the DRG1248-268 epitope of DRG-1 was required for T cell recognition. Reverse transcription-polymerase chain reaction revealed that DRG-1 was highly expressed in melanoma cell lines but not in normal tissues. DRG-1 knockdown by lentiviral-based shRNA suppressed melanoma cell proliferation and soft agar colony formation. Taken together, these data suggest that DRG-1 plays an important role in melanoma cell growth and transformation, indicating that DRG1 may represent a novel target for CD4(+) T cell-mediated immunotherapy in melanoma.
authors.affiliation: Center for Cell and Gene Therapy, Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kiniwa
authors.affiliation: Center for Cell and Gene Therapy, Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Jiang
authors.initials: J
authors.lastname: Li
authors.affiliation: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, Texas, United States of America.
authors.forename: Mingjun
authors.initials: M
authors.lastname: Wang
authors.affiliation: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, Texas, United States of America.
authors.forename: Chuang
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Surgical Oncology, UT MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Center for Cell and Gene Therapy, Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, United States of America; Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, Texas, United States of America.
authors.forename: Rong-Fu
authors.initials: RF
authors.lastname: Wang
authors.affiliation: Center for Cell and Gene Therapy, Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, United States of America; Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, Texas, United States of America.
authors.forename: Helen Y
authors.initials: HY
authors.lastname: Wang
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000276:immunology*; D059810:HLA-DR Serological Subtypes / Q000276:immunology; D006801:Humans; D008545:Melanoma / Q000276:immunology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D059810:HLA-DR Serological Subtypes; C080766:HLA-DR11 antigen; D034741:RNA, Small Interfering; C078418:developmentally regulated GTP-binding protein; D019204:GTP-Binding Proteins