CMC-544 (inotuzumab ozogamicin) shows less effect on multidrug resistant cells: Analyses in cell lines and cells from patients with B-cell chronic lymphocytic leukaemia and lymphoma

Akihiro Takeshita, Kaori Shinjo, Nozomi Yamakage, Takaaki Ono, Isao Hirano, Hirotaka Matsui, Kazuyuki Shigeno, Satoki Nakamura, Tadasu Tobita, Masato Maekawa, Kazunori Ohnishi, Yoshikazu Sugimoto, Hitoshi Kiyoi, Tomoki Naoe, Ryuzo Ohno

研究成果: Article

39 引用 (Scopus)

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The effect of CMC-544, a calicheamicin-conjugated anti-CD22 monoclonal antibody, was analysed in relation to CD22 and P-glycoprotein (P-gp) in B-cell chronic lymphocytic leukaemia (CLL) and non-Hodgkin lymphoma (NHL) in vitro. The cell lines used were CD22-positive parental Daudi and Raji, and their P-gp positive sublines, Daudi/MDR and Raji/MDR. Cells obtained from 19 patients with B-cell CLL or NHL were also used. The effect of CMC-544 was analysed by viable cell count, morphology, annexin-V staining, and cell cycle distribution. A dose-dependent, selective cytotoxic effect of CMC-544 was observed in cell lines that expressed CD22. CMC-544 was not effective on Daudi/MDR and Raji/MDR cells compared with their parental cells. The MDR modifiers, PSC833 and MS209, restored the cytotoxic effect of CMC-544 in P-gp-expressing sublines. In clinical samples, the cytotoxic effect of CMC-544 was inversely related to the amount of P-gp (P = 0·003), and to intracellular rhodamine-123 accumulation (P < 0·001). On the other hand, the effect positively correlated with the amount of CD22 (P = 0·010). The effect of CMC-544 depends on the levels of CD22 and P-gp. Our findings will help to predict the clinical effectiveness of this drug on these B-cell malignancies, suggesting a beneficial effect with combined use of CMC-544 and MDR modifiers.

元の言語English
ページ(範囲)34-43
ページ数10
ジャーナルBritish Journal of Haematology
146
発行部数1
DOI
出版物ステータスPublished - 2009 7 1

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ASJC Scopus subject areas

  • Hematology

これを引用

Takeshita, A., Shinjo, K., Yamakage, N., Ono, T., Hirano, I., Matsui, H., Shigeno, K., Nakamura, S., Tobita, T., Maekawa, M., Ohnishi, K., Sugimoto, Y., Kiyoi, H., Naoe, T., & Ohno, R. (2009). CMC-544 (inotuzumab ozogamicin) shows less effect on multidrug resistant cells: Analyses in cell lines and cells from patients with B-cell chronic lymphocytic leukaemia and lymphoma. British Journal of Haematology, 146(1), 34-43. https://doi.org/10.1111/j.1365-2141.2009.07701.x