Back to Search
Start Over
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.
- Source :
- British Journal of Haematology; Jul2009, Vol. 146 Issue 1, p34-43, 10p, 1 Chart, 3 Graphs
- Publication Year :
- 2009
-
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. [ABSTRACT FROM AUTHOR]
- Subjects :
- LYMPHOCYTIC leukemia
CELL lines
LYMPHOMAS
HODGKIN'S disease
B cells
Subjects
Details
- Language :
- English
- ISSN :
- 00071048
- Volume :
- 146
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- British Journal of Haematology
- Publication Type :
- Academic Journal
- Accession number :
- 41330373
- Full Text :
- https://doi.org/10.1111/j.1365-2141.2009.07701.x