Carbonic anhydrase II is a tumor vessel endothelium-associated antigen targeted by dendritic cell therapy

Kenta Yoshiura, Takashi Nakaoka, Toshihide Nishishita, Katsuaki Sato, Akifumi Yamamoto, Shinji Shimada, Toshiaki Saida, Yutaka Kawakami, Tsuneo A. Takahashi, Hiroyuki Fukuda, Shinobu Imajoh-Ohmi, Naoki Oyaizu, Naohide Yamashita

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44 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)8201-8207
Number of pages7
JournalClinical Cancer Research
Volume11
Issue number22
DOIs
Publication statusPublished - 2005 Nov 15

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Yoshiura, K., Nakaoka, T., Nishishita, T., Sato, K., Yamamoto, A., Shimada, S., Saida, T., Kawakami, Y., Takahashi, T. A., Fukuda, H., Imajoh-Ohmi, S., Oyaizu, N., & Yamashita, N. (2005). Carbonic anhydrase II is a tumor vessel endothelium-associated antigen targeted by dendritic cell therapy. Clinical Cancer Research, 11(22), 8201-8207. https://doi.org/10.1158/1078-0432.CCR-05-0816