RT Journal Article
SR Electronic
T1 Efficacy, Biodistribution, and Pharmacokinetics of CD22-Targeted Pegylated Liposomal Doxorubicin in a B-cell Non–Hodgkin's Lymphoma Xenograft Mouse Model
JF Clinical Cancer Research
JO Clin Cancer Res
FD American Association for Cancer Research
SP 2760
OP 2768
DO 10.1158/1078-0432.CCR-09-3199
VO 16
IS 10
A1 Tuscano, Joseph M.
A1 Martin, Shiloh M.
A1 Ma, Yunpeng
A1 Zamboni, William
A1 O'Donnell, Robert T.
YR 2010
UL http://clincancerres.aacrjournals.org/content/16/10/2760.abstract
AB Purpose: Non–Hodgkin's lymphoma (NHL) is the sixth most common cause of cancer death in the U.S. Pegylated liposomal doxorubicin (PLD) is a liposomal form of doxorubicin (DXR) that causes less toxicity than does free DXR. To further enhance efficacy and decrease toxicity, we conjugated HB22.7, an anti-CD22 monoclonal antibody to PLD, thus creating CD22-targeted immunoliposomal PLD (IL-PLD).Experimental Design: In vitro cytotoxicity of IL-PLD and PLD was assessed in CD22-positive and CD22-negative cell lines. Biodistribution, myelotoxicity, and plasma pharmacokinetics were measured in NHL xenograft–bearing mice treated with IL-PLD or PLD. Survival, tumor volume, and toxicity (WBC counts, body weights) were assessed in mice receiving a single dose (8, 12, or 16 mg DXR/kg) or three doses (8 mg DXR/kg/dose) of IL-PLD; controls were PLD, free DXR, PLD plus unconjugated HB22.7, IL-null (HB22.7-conjugated empty liposome), and nontreated mice.Results: IL-PLD improved cytotoxicity over PLD only in CD22-positive cells. IL-PLD displayed similar pharmacokinetics and toxicities as PLD. Tumor DXR accumulation was greater and tumor/normal tissue ratios were similar (spleen) or greater (kidney, lung, and liver) in mice treated with IL-PLD versus PLD. IL-PLD reduced tumor volume more effectively than PLD at all doses; the three-dose regimen was superior. The three-dose regimen was used in confirmatory studies, which showed that IL-PLD produced significantly greater tumor volume reduction and enhanced survival versus PLD.Conclusion: IL-PLD has increased efficacy without increased toxicity compared with PLD. This suggests that IL-PLD may be an improved form of DXR-based therapy of NHL. Clin Cancer Res; 16(10); 2760–8. ©2010 AACR.