| RRC ID |
37678
|
| 著者 |
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.
|
| タイトル |
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.
|
| ジャーナル |
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.
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| 巻・号 |
146(1)
|
| ページ |
34-43
|
| 公開日 |
2009-6-1
|
| DOI |
10.1111/j.1365-2141.2009.07701.x
|
| PII |
BJH7701
|
| 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
|
| 引用数 |
39
|
|
WOS 分野
|
HEMATOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
K562
Jurkat(RCB0806) |
