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.
| Original language | English |
|---|---|
| Pages (from-to) | 34-43 |
| Number of pages | 10 |
| Journal | British Journal of Haematology |
| Volume | 146 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2009 Jul |
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Keywords
- Calicheamicin
- CD22
- CMC-544
- Monoclonal antibody
- P-glycoprotein
ASJC Scopus subject areas
- Hematology
Cite this
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. / Takeshita, Akihiro; Shinjo, Kaori; Yamakage, Nozomi; Ono, Takaaki; Hirano, Isao; Matsui, Hirotaka; Shigeno, Kazuyuki; Nakamura, Satoki; Tobita, Tadasu; Maekawa, Masato; Ohnishi, Kazunori; Sugimoto, Yoshikazu; Kiyoi, Hitoshi; Naoe, Tomoki; Ohno, Ryuzo.
In: British Journal of Haematology, Vol. 146, No. 1, 07.2009, p. 34-43.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CMC-544 (inotuzumab ozogamicin) shows less effect on multidrug resistant cells
T2 - Analyses in cell lines and cells from patients with B-cell chronic lymphocytic leukaemia and lymphoma
AU - Takeshita, Akihiro
AU - Shinjo, Kaori
AU - Yamakage, Nozomi
AU - Ono, Takaaki
AU - Hirano, Isao
AU - Matsui, Hirotaka
AU - Shigeno, Kazuyuki
AU - Nakamura, Satoki
AU - Tobita, Tadasu
AU - Maekawa, Masato
AU - Ohnishi, Kazunori
AU - Sugimoto, Yoshikazu
AU - Kiyoi, Hitoshi
AU - Naoe, Tomoki
AU - Ohno, Ryuzo
PY - 2009/7
Y1 - 2009/7
N2 - 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.
AB - 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.
KW - Calicheamicin
KW - CD22
KW - CMC-544
KW - Monoclonal antibody
KW - P-glycoprotein
UR - http://www.scopus.com/inward/record.url?scp=66949176946&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=66949176946&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2141.2009.07701.x
DO - 10.1111/j.1365-2141.2009.07701.x
M3 - Article
C2 - 19388933
AN - SCOPUS:66949176946
VL - 146
SP - 34
EP - 43
JO - British Journal of Haematology
JF - British Journal of Haematology
SN - 0007-1048
IS - 1
ER -