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 (R) (commercial doxorubicin-loaded liposomes) and that of Doxil (R) conjugated with anti-CD30 antibodies (CD30-targeted Doxil (R)) in treating anaplastic large cell lymphoma (ALCL), a type of T-cell lymphoma characterized by a high CD30 expression. Compared to Doxil (R), the CD30-targeted Doxil (R) 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 mu g/mL versus 12.6 mu g/ml, p = 0.006). In a SCID mouse xenograft model, CD30-targeted Doxil (R) inhibited tumor growth more significantly than the unconjugated formulation; specifically, tumors in mice treated with CD30-targeted Doxil (R) were significantly smaller than those in mice treated with Doxil (R) (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. (C) 2013 Elsevier Ltd. All rights reserved.