Identification of BING-4 cancer antigen translated from an alternative open reading frame of a gene in the extended MHC class II region using lymphocytes from a patient with a durable complete regression following immunotherapy.
Multiple human cancer Ags have been identified, although little is known concerning which would be most effectively used in cancer immunotherapy. To gain insight into the selection of appropriate Ags, the immunologic reactivity of a patient who had a durable complete regression of melanoma metastases was measured. PBMCs were directly cloned using the monoclonal anti-CD3 Ab OKT3 and IL-2 without any bias introduced by previous culture. A lymphocyte clone recognized a previously unknown shared melanoma Ag that was identified as the BING-4 protein encoded in a gene-rich region of the extended class II MHC. The HLA-A2-restricted BING-4 immunodominant peptide was translated from a 10-aa-long alternative open reading frame. In vitro sensitization against this peptide generated lymphocytes reactive against HLA-A2(+) melanomas. Real-time semiquantitative RT-PCR analysis revealed that 8 of 15 melanoma cell lines overexpressed BING-4, and this correlated with recognition by lymphocytes. Overexpression was not found in normal tissues or other tumor types. Thus, BING-4 represents another candidate Ag for possible use in the immunotherapy of patients with melanoma.
Rosenberg
Steven A
SA
Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room 2B42, Bethesda, MD 20892, USA. sar@nih.gov
Tong-On
Panida
P
Li
Yong
Y
Riley
John P
JP
El-Gamil
Mona
M
Parkhurst
Maria R
MR
Robbins
Paul F
PF
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D002460:Cell Line; D002999:Clone Cells; D003001:Cloning, Molecular; D005802:Genes, MHC Class II; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D016366:Open Reading Frames; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D010455:Peptides; D012333:RNA, Messenger; C449187:WDR46 protein, human; D007371:Interferon-gamma