RRC ID 37678
Author 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.
Title 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.
Journal Br J Haematol
Abstract 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.
Volume 146(1)
Pages 34-43
Published 2009-6-1
DOI 10.1111/j.1365-2141.2009.07701.x
PMID 19388933
MeSH ATP Binding Cassette Transporter, Subfamily B, Member 1 / analysis ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism Antibodies, Monoclonal / therapeutic use* Antibodies, Monoclonal, Humanized Antineoplastic Agents / therapeutic use* Cell Count Cell Line, Transformed Cell Line, Tumor Cyclosporins / therapeutic use Dose-Response Relationship, Drug Drug Resistance, Multiple / drug effects Drug Resistance, Neoplasm Flow Cytometry Humans Immunosuppressive Agents / therapeutic use Inotuzumab Ozogamicin Jurkat Cells Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy* Leukemia, Lymphocytic, Chronic, B-Cell / immunology Leukemia, Lymphocytic, Chronic, B-Cell / metabolism Lymphoma, Non-Hodgkin / drug therapy* Lymphoma, Non-Hodgkin / immunology Lymphoma, Non-Hodgkin / metabolism Quinolines / therapeutic use Sialic Acid Binding Ig-like Lectin 2 / analysis Sialic Acid Binding Ig-like Lectin 2 / immunology Treatment Outcome Tumor Cells, Cultured
IF 5.518
Times Cited 39
Human and Animal Cells K562 Jurkat(RCB0806)