Abstract

Abstract Current cancer therapies have shown limited success due to the poor selectivity. The recent chemotherapy could be far more effective if higher doses could be specifically delivered to the tumor and not to normal tissues. Therefore a reliable tumor specific therapy is urgently needed to treat cancer patients. Targeted nanoparticle can attenuate the off-target toxicity and enhance the efficacy of existing therapies, which would be highly beneficial to the cancer patients. In spite of a lot of effort still the optimal formulation of nanoparticle for the actual translational applications was not established yet. Liposomes, unilamellar vesicles composed of natural and/or synthetic lipids have been an intensively studied system. By refining the early formulations and after extensive testing, recently we could invent a new type of lipid bilayer nanoparticle delivery system, HPLN (Hybrid Polymerized Liposomal Nanoparticles) and demonstrate that this new type of polymeric nanoparticle overcomes many, if not most, of the deficiencies noted and has tremendous potential as an effective delivery vehicle for treating many types of cancer. In our study it was shown that the targeted HPLN with human antibodies (antiCD99 or antiCD19) can inhibit the growth of Ewing's sarcoma and leukemia (ALL) in a murine model. The antitumor effects of of HPLN were diminished pretty much by the removal of antibody or drug (Doxorubicin), which proves efficacy of the targeted HPLNs is specifically dependent upon the targeting antibody and drug. In addition, no abnormalities in liver and kidney function tests, complete blood counts or pathology of major organs are observed from tail-vein administrations. These data provide strong evidence for the safety and efficacy of this targeted HPLN delivery system of anticancer drugs to Ewing's sarcoma and leukemia (ALL). In conclusion, our result showed a potential of targeted HPLN as a selective delivery vehicle of cytotoxic drugs to cancers. Hopefully this technology will be applied to treat many other different types of tumor cells in the future. Citation Format: Hyunggyoo Kang, Jon Nagy, Timothy Trivhe. Targeted therapy of leukemia and Ewing's sarcoma by human antibody-targeted nanoparticles. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2695.

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