Anti-CD30 antibody conjugated liposomal doxorubicin with significantly improved therapeutic efficacy against anaplastic large cell lymphoma

Abstract

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.

Keywords: Anaplastic large cell lymphoma; CD30; Doxorubicin; Liposome; Targeted therapy.