Carbonic Anhydrase II Is a Tumor Vessel Endothelium–Associated Antigen Targeted by Dendritic Cell Therapy
| Autor: | Shinji Shimada, Yutaka Kawakami, Takashi Nakaoka, Hiroyuki Fukuda, Kenta Yoshiura, Naohide Yamashita, Toshihide Nishishita, Toshiaki Saida, Akifumi Yamamoto, Shinobu Imajoh-Ohmi, Tsuneo A. Takahashi, Katsuaki Sato, Naoki Oyaizu |
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| Rok vydání: | 2005 |
| Předmět: |
Adult
Male Cancer Research Pathology medicine.medical_specialty Antibodies Neoplasm medicine.medical_treatment Carbonic anhydrase II Molecular Sequence Data Neovascularization Physiologic Biology Carbonic Anhydrase II Immunotherapy Adoptive Gene Expression Regulation Enzymologic Cell Line Cell therapy Antigen Antigens Neoplasm Cell Line Tumor medicine Humans Electrophoresis Gel Two-Dimensional Amino Acid Sequence RNA Messenger Antigen-presenting cell Melanoma Aged Reverse Transcriptase Polymerase Chain Reaction Endothelial Cells Dendritic Cells Immunotherapy Dendritic cell Middle Aged medicine.disease Immunohistochemistry Molecular Weight Oncology Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Female Endothelium Vascular |
| Zdroj: | Clinical Cancer Research. 11:8201-8207 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-05-0816 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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