(137c) Synergistic and Multimodal Cancer Gene Therapy Using Viral/Nonviral Chimeric Vectors
AIChE Annual Meeting
Monday, November 11, 2019 - 1:06pm to 1:24pm
As a therapeutic model, Ph+ leukemia, caused by a Bcr-Abl translocation, was explored. Bcr-Abl translocation causes down-regulation in the pro-apoptotic gene Bim and up-regulation in the pro-survival gene Mcl-1. To treat Ph+ leukemia, Bim expressing AAV and Mcl-1 silencing siRNA were encapsulated in the ketalized shell. Bim expression and Mcl-1 down-regulation synergistically induced apoptosis and suppressed proliferation, specifically in diseased cells. To enhance the efficacy of the hybrid system, the tyrosine kinase inhibitor, dasatinib (current standard of care for Ph+ leukemia), was co-delivered with the particles. The combined delivery of particles with dasatinib acted synergistically, and allowed for much smaller doses of the drug for the same effect. The smaller dosage reduces the risk of acquired resistance to dasatinib and presents a possibility to permanently cure leukemia, instead of just stopping disease progression. This talk will detail the creation of hybrid particles and their use as a specific and effective treatment alone, or in combination with dasatinib, against a Ph+ leukemia and potentially other cancers.