(572bl) Antisense Oligonucleotides (As ODNs) Based Leuckemia Therapy Using Therapeutic Antibody Conjugated Nano-Lipopolyplexes (NLPs)

CD20 antibody is a FDA-approved therapeutic antibody that has been used in clinical treatment for leukemia. In this study, we conjugated antiCD20 on nano-lipopolyplexes (NLP) carrying Bcl-2 targeted antisense oligonucleotide (AS-ODN) for enhancing delivery to leukemia cells. In comparison to free ODN, the formulated ODN in antiCD20-NLP showed preferential uptake by B leukemia cells. The uptake of AS ODN correlated well with the CD20 expression levels on the cells. antiCD20-NLP mediated ODN delivery can enhance the intracellular Bcl-2 down-regulation in both B cell lines, such as Raji, and leukemia patient cells. The uptake and intracellular trafficking of ODN loaded antiCD20-NLP were characterized by confocal microscopy and Quantum Dot-FRET technology. We also found that the antiCD20 conjugated to NLPs can induce apoptosis on primary leukemia cells by the CD20 cross-linking mechanism. Our findings provide a new approach to improving the clinical efficacy of AS-ODNs therapy in treatment of B cell malignancies. The same approach can also be applied to therapeutic antibodies mediated small interfering RNA (siRNA) delivery for leukemia and other B cell related malignancies.