Anti-CD30 antibody conjugated liposomal doxorubicin with significantly improved therapeutic efficacy against anaplastic large cell lymphoma.
The use of nano-carriers has been shown to improve the delivery and efficacy of chemotherapeutic agents in cancer patients. Recent studies suggest that decoration of the surface of nano-carriers with various targeting moieties may further improve the overall therapeutic efficacy. In this study, we compared the therapeutic efficacy of Doxil(®) (commercial doxorubicin-loaded liposomes) and that of Doxil(®) conjugated with anti-CD30 antibodies (CD30-targeted Doxil(®)) in treating anaplastic large cell lymphoma (ALCL), a type of T-cell lymphoma characterized by a high CD30 expression. Compared to Doxil(®), the CD30-targeted Doxil(®) showed a significantly higher binding affinity to ALCL cells (5.3% versus 27%, p = 0.005) and a lower inhibitory concentration at 50% (IC50) in-vitro (32.6 μg/mL versus 12.6 μg/mL, p = 0.006). In a SCID mouse xenograft model, CD30-targeted Doxil(®) inhibited tumor growth more significantly than the unconjugated formulation; specifically, tumors in mice treated with CD30-targeted Doxil(®) were significantly smaller than those in mice treated with Doxil(®) (average, 117 mm(3) versus 270 mm(3), p = 0.001) at 18 days after the tumors were inoculated. Our findings have provided the proof-of-principle of using CD30-targeted nano-carriers to treat cancers that are characterized by a high level of CD30 expression, such as ALCL.
Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.|School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
Ommoleila
O
Molavi
Faculty of Pharmacy and Pharmaceutical Science, University of Alberta, Edmonton, Alberta, Canada.
Xiao-Bing
XB
Xiong
Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
Donna
D
Douglas
Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
Norm
N
Kneteman
Cancer Biology Research Center, Sanford Research/USD, SD, USA.
Satoshi
S
Nagata
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Ira
I
Pastan
Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
Quincy
Q
Chu
Faculty of Pharmacy and Pharmaceutical Science, University of Alberta, Edmonton, Alberta, Canada.
Afsaneh
A
Lavasanifar
Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.|Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
Raymond
R
Lai
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017730:Ki-1 Antigen / Q000276:immunology*; D017728:Lymphoma, Large-Cell, Anaplastic / Q000188:drug therapy*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D053758:Nanoparticles / Q000737:chemistry; D011092:Polyethylene Glycols / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D017730:Ki-1 Antigen; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin
Anaplastic large cell lymphoma; CD30; Doxorubicin; Liposome; Targeted therapy