title: Carbonic anhydrase II is a tumor vessel endothelium-associated antigen targeted by dendritic cell therapy.
abstract: Tumor-associated antigens are promising candidates as target molecules for immunotherapy and a wide variety of tumor-associated antigens have been discovered through the presence of serum antibodies in cancer patients. We previously conducted dendritic cell therapy on 10 malignant melanoma patients and shrinkage or disappearance of metastatic tumors with massive necrosis occurred in two patients. In this study, we found a 29-kDa protein against which antibody was elicited by dendritic cell therapy in one of the two patients. Matrix-assisted laser desorption ionization-time of flight/mass spectrometry analysis of the protein isolated by two-dimensional electrophoresis combined with Western blots revealed that the 29-kDa protein was carbonic anhydrase II (CA-II). Immunohistochemistry of the tumors and normal tissues showed that CA-II was expressed in the tumor vessel but not in normal vessel endothelium. CA-II expression in tumor endothelium was observed as well in other cancers including esophageal, renal, and lung cancers. In an in vitro angiogenesis model, CA-II expression of normal human vein endothelial cells was significantly up-regulated when cells were cultured in the acidic and hypoxic conditions indicative of a tumor environment. These findings suggest that CA-II is a tumor vessel endothelium-associated antigen in melanoma and other cancers, and elicitation of serum anti-CA-II antibody by dendritic cell therapy may be associated with good clinical outcome including tumor reduction.
authors.affiliation: Department of Advanced Medical Science, University of Tokyo, Japan. yoshiura-gi@umin.ac.jp.
authors.forename: Kenta
authors.initials: K
authors.lastname: Yoshiura
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakaoka
authors.forename: Toshihide
authors.initials: T
authors.lastname: Nishishita
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Sato
authors.forename: Akifumi
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Shinji
authors.initials: S
authors.lastname: Shimada
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Saida
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Tsuneo A
authors.initials: TA
authors.lastname: Takahashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fukuda
authors.forename: Shinobu
authors.initials: S
authors.lastname: Imajoh-Ohmi
authors.forename: Naoki
authors.initials: N
authors.lastname: Oyaizu
authors.forename: Naohide
authors.initials: N
authors.lastname: Yamashita
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000912:Antibodies, Neoplasm / Q000097:blood; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology; D024402:Carbonic Anhydrase II / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D015180:Electrophoresis, Gel, Two-Dimensional; D042783:Endothelial Cells / Q000201:enzymology / Q000502:physiology; D004730:Endothelium, Vascular / Q000276:immunology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007150:Immunohistochemistry; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D008969:Molecular Sequence Data; D008970:Molecular Weight; D018919:Neovascularization, Physiologic / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D012333:RNA, Messenger; D024402:Carbonic Anhydrase II