Carbonic Anhydrase II Is a Tumor Vessel Endothelium–Associated Antigen Targeted by Dendritic Cell Therapy

• Published in: Clinical cancer research Vol. 11; no. 22; pp. 8201 - 8207
• Main Authors: YOSHIURA, Kenta, NAKAOKA, Takashi, IMAJOH-OHMI, Shinobu, OYAIZU, Naoki, YAMASHITA, Naohide, NISHISHITA, Toshihide, SATO, Katsuaki, YAMAMOTO, Akifumi, SHIMADA, Shinji, SAIDA, Toshiaki, KAWAKAMI, Yutaka, TAKAHASHI, Tsuneo A, FUKUDA, Hiroyuki
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-11-2005
• Subjects: Adult; Aged; Amino Acid Sequence; Antibodies, Neoplasm - blood; Antigens, Neoplasm - chemistry; Antigens, Neoplasm - immunology; Antineoplastic agents; Biological and medical sciences; Carbonic Anhydrase II - chemistry; Carbonic Anhydrase II - genetics; Carbonic Anhydrase II - immunology; Cell Line; Cell Line, Tumor; Dendritic Cells - immunology; Dendritic Cells - transplantation; Electrophoresis, Gel, Two-Dimensional; Endothelial Cells - enzymology; Endothelial Cells - physiology; Endothelium, Vascular - immunology; Female; Gene Expression Regulation, Enzymologic; Humans; Immunohistochemistry; Immunotherapy, Adoptive - methods; Male; Medical sciences; Melanoma - immunology; Melanoma - pathology; Melanoma - therapy; Melanoma/skin cancers; Middle Aged; Molecular Sequence Data; Molecular Weight; Neovascularization, Physiologic - physiology; Pharmacology. Drug treatments; Proteomics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tumor Angiogenesis and Microcirculation; Tumor antigens; Tumor immunobiology; Dendritic cell; Cell therapy; Enzyme; Lyases; Malignant tumor; Endothelium; Antigen; Antigen presenting cell; Blood vessel; Carbonate dehydratase; Circulatory system; Target cell; Carbon-oxygen lyases; Hydro-lyases
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-05-0816

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.