Humanized anti-CD26 monoclonal antibody as a treatment for malignant mesothelioma tumors

Teruo Inamoto, Taketo Yamada, Kei Ohnuma, Shinichiro Kina, Nozomu Takahashi, Tadanori Yamochi, Sakiko Inamoto, Yoji Katsuoka, Osamu Hosono, Hirotoshi Tanaka, Nam H. Dang, Chikao Morimoto

研究成果: Article

59 引用 (Scopus)

抄録

Purpose: CD26 is a 110-kDa cell surface antigen with a role in tumor development. In this report, we show that CD26 is highly expressed on the cell surface of malignant mesothelioma and that a newly developed humanized anti-CD26 monoclonal antibody (mAb) has an inhibitory effect on malignant mesothelioma cells in both in vitro and in vivo experiments. Experimental Design: Using immunohistochemistry, 12 patients' surgical specimens consisting of seven malignant mesothelioma, three reactive mesothelial cells, and two adenomatoid tumors were evaluated for expression of CD26. The effects of CD26 on malignant mesothelioma cells were assessed in the presence of transfection of CD26-expressing plasmid, humanized anti-CD26 mAb, or small interfering RNA against CD26. The in vivo growth inhibitory effect of humanized anti-CD26 mAb was assessed in human malignant mesothelioma cell mouse xenograft models. Results: In surgical specimens, CD26 is highly expressed in malignant mesothelioma but not in benign mesothelial tissues. Depletion of CD26 by small interfering RNA results in the loss of adhesive property, suggesting that CD26 is a binding protein to the extracellular matrix. Moreover, our in vitro data indicate that humanized anti-CD26 mAb induces cell lysis of malignant mesothelioma cells via antibody-dependent cell-mediated cytotoxicity in addition to its direct anti-tumor effect via p27kip1 accumulation. In vivo experiments with mouse xenograft models involving human malignant mesothelioma cells show that humanized anti-CD26 mAb treatment drastically inhibits tumor growth in tumor-bearing mice, resulting in enhanced survival. Conclusions: Our data strongly suggest that humanized anti-CD26 mAb treatment may have potential clinical use as a novel cancer therapeutic agent in CD26-positive malignant mesothelioma.

元の言語English
ページ(範囲)4191-4200
ページ数10
ジャーナルClinical Cancer Research
13
発行部数14
DOI
出版物ステータスPublished - 2007 7 15

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Monoclonal Antibodies
Neoplasms
Therapeutics
Heterografts
Small Interfering RNA
Adenomatoid Tumor
Antibody-Dependent Cell Cytotoxicity
Malignant Mesothelioma
Surface Antigens
Growth
Adhesives
Extracellular Matrix
Transfection
Carrier Proteins
Plasmids
Research Design
Epithelium
Immunohistochemistry
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

これを引用

Inamoto, T., Yamada, T., Ohnuma, K., Kina, S., Takahashi, N., Yamochi, T., ... Morimoto, C. (2007). Humanized anti-CD26 monoclonal antibody as a treatment for malignant mesothelioma tumors. Clinical Cancer Research, 13(14), 4191-4200. https://doi.org/10.1158/1078-0432.CCR-07-0110

Humanized anti-CD26 monoclonal antibody as a treatment for malignant mesothelioma tumors. / Inamoto, Teruo; Yamada, Taketo; Ohnuma, Kei; Kina, Shinichiro; Takahashi, Nozomu; Yamochi, Tadanori; Inamoto, Sakiko; Katsuoka, Yoji; Hosono, Osamu; Tanaka, Hirotoshi; Dang, Nam H.; Morimoto, Chikao.

:: Clinical Cancer Research, 巻 13, 番号 14, 15.07.2007, p. 4191-4200.

研究成果: Article

Inamoto, T, Yamada, T, Ohnuma, K, Kina, S, Takahashi, N, Yamochi, T, Inamoto, S, Katsuoka, Y, Hosono, O, Tanaka, H, Dang, NH & Morimoto, C 2007, 'Humanized anti-CD26 monoclonal antibody as a treatment for malignant mesothelioma tumors', Clinical Cancer Research, 巻. 13, 番号 14, pp. 4191-4200. https://doi.org/10.1158/1078-0432.CCR-07-0110
Inamoto T, Yamada T, Ohnuma K, Kina S, Takahashi N, Yamochi T その他. Humanized anti-CD26 monoclonal antibody as a treatment for malignant mesothelioma tumors. Clinical Cancer Research. 2007 7 15;13(14):4191-4200. https://doi.org/10.1158/1078-0432.CCR-07-0110
Inamoto, Teruo ; Yamada, Taketo ; Ohnuma, Kei ; Kina, Shinichiro ; Takahashi, Nozomu ; Yamochi, Tadanori ; Inamoto, Sakiko ; Katsuoka, Yoji ; Hosono, Osamu ; Tanaka, Hirotoshi ; Dang, Nam H. ; Morimoto, Chikao. / Humanized anti-CD26 monoclonal antibody as a treatment for malignant mesothelioma tumors. :: Clinical Cancer Research. 2007 ; 巻 13, 番号 14. pp. 4191-4200.
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abstract = "Purpose: CD26 is a 110-kDa cell surface antigen with a role in tumor development. In this report, we show that CD26 is highly expressed on the cell surface of malignant mesothelioma and that a newly developed humanized anti-CD26 monoclonal antibody (mAb) has an inhibitory effect on malignant mesothelioma cells in both in vitro and in vivo experiments. Experimental Design: Using immunohistochemistry, 12 patients' surgical specimens consisting of seven malignant mesothelioma, three reactive mesothelial cells, and two adenomatoid tumors were evaluated for expression of CD26. The effects of CD26 on malignant mesothelioma cells were assessed in the presence of transfection of CD26-expressing plasmid, humanized anti-CD26 mAb, or small interfering RNA against CD26. The in vivo growth inhibitory effect of humanized anti-CD26 mAb was assessed in human malignant mesothelioma cell mouse xenograft models. Results: In surgical specimens, CD26 is highly expressed in malignant mesothelioma but not in benign mesothelial tissues. Depletion of CD26 by small interfering RNA results in the loss of adhesive property, suggesting that CD26 is a binding protein to the extracellular matrix. Moreover, our in vitro data indicate that humanized anti-CD26 mAb induces cell lysis of malignant mesothelioma cells via antibody-dependent cell-mediated cytotoxicity in addition to its direct anti-tumor effect via p27kip1 accumulation. In vivo experiments with mouse xenograft models involving human malignant mesothelioma cells show that humanized anti-CD26 mAb treatment drastically inhibits tumor growth in tumor-bearing mice, resulting in enhanced survival. Conclusions: Our data strongly suggest that humanized anti-CD26 mAb treatment may have potential clinical use as a novel cancer therapeutic agent in CD26-positive malignant mesothelioma.",
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AU - Inamoto, Teruo

AU - Yamada, Taketo

AU - Ohnuma, Kei

AU - Kina, Shinichiro

AU - Takahashi, Nozomu

AU - Yamochi, Tadanori

AU - Inamoto, Sakiko

AU - Katsuoka, Yoji

AU - Hosono, Osamu

AU - Tanaka, Hirotoshi

AU - Dang, Nam H.

AU - Morimoto, Chikao

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Y1 - 2007/7/15

N2 - Purpose: CD26 is a 110-kDa cell surface antigen with a role in tumor development. In this report, we show that CD26 is highly expressed on the cell surface of malignant mesothelioma and that a newly developed humanized anti-CD26 monoclonal antibody (mAb) has an inhibitory effect on malignant mesothelioma cells in both in vitro and in vivo experiments. Experimental Design: Using immunohistochemistry, 12 patients' surgical specimens consisting of seven malignant mesothelioma, three reactive mesothelial cells, and two adenomatoid tumors were evaluated for expression of CD26. The effects of CD26 on malignant mesothelioma cells were assessed in the presence of transfection of CD26-expressing plasmid, humanized anti-CD26 mAb, or small interfering RNA against CD26. The in vivo growth inhibitory effect of humanized anti-CD26 mAb was assessed in human malignant mesothelioma cell mouse xenograft models. Results: In surgical specimens, CD26 is highly expressed in malignant mesothelioma but not in benign mesothelial tissues. Depletion of CD26 by small interfering RNA results in the loss of adhesive property, suggesting that CD26 is a binding protein to the extracellular matrix. Moreover, our in vitro data indicate that humanized anti-CD26 mAb induces cell lysis of malignant mesothelioma cells via antibody-dependent cell-mediated cytotoxicity in addition to its direct anti-tumor effect via p27kip1 accumulation. In vivo experiments with mouse xenograft models involving human malignant mesothelioma cells show that humanized anti-CD26 mAb treatment drastically inhibits tumor growth in tumor-bearing mice, resulting in enhanced survival. Conclusions: Our data strongly suggest that humanized anti-CD26 mAb treatment may have potential clinical use as a novel cancer therapeutic agent in CD26-positive malignant mesothelioma.

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