Abstract
Abstract Poor selectivity of the current cancer therapies causes a variety of side effects such as secondary cancers, heart or lung damage, infertility or chronic hepatitis. Therefore a reliable tumor specific therapy is urgently needed to treat cancer patients. It has been widely recognized that the recent chemotherapy could be far more effective if higher doses could be specifically delivered to the tumor and not to normal tissues. Targeted nanoparticles have shown the potential to deliver anticancer drugs to cancer cells selectively and thus to overcome unexpected cytotoxicity and limited efficacy of the chemotherapy caused by the unselective delivery to normal cells. However in addition to the selectivity the efficacy of the targeted nanoparticles depends upon two more requirements: immune evasion and timely release of contents in target cells. In spite of a lot of effort still the optimal formulation of nanoparticle for the actual translational applications was not established yet. PLN (Polymerized Liposomal Nanoparticles) can be synthesized to a variety of physiochemical properties including a broad range of composition and size. By refining the early formulations and after extensive testing, recently we could invent 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 antibodies (antiCD99 or antiCD19) can inhibit the growth of Ewing's sarcoma and childhood leukemia (ALL) in a murine model. The antitumor effects 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 childhood 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, Violette Shahbazian, Ryan Holly, Jon Nagy, Timothy Triche. Targeted therapy of Ewing's Sarcoma and childhood leukemia (ALL) by hybrid polymerized liposomal nanoparticles (HPLN). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1623. doi:10.1158/1538-7445.AM2015-1623
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