Until now a lot of understanding and research of cancer biology can make it possible to develop many anticancer drugs which can inhibit the specific pathways required for growth, proliferation, and survival of cancer cells. The current success in cancer therapy using these drugs improves the survival rate of patients but unfortunately it is not the case of all cancers and still many different kinds of cancers continue to have a poor prognosis. Furthermore the incompleteness of 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 is 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 the anticancer drugs to cancer cells selectively and to overcome unexpected cytotoxicity and limited efficacy of the chemotherapy caused by the unselective delivery to the normal cells. In our study a novel nanoparticle (HPLN) was used for the treatment of childhood ALL and Ewing's sarcoma. AntiCD19 and antiCD99 antibodies were used for targeting of ALL and Ewing tumor, respectively. These tumor specific HPLNs effectively inhibit tumor growth in a murine model. Removal of targeting antibody or drug eliminates the antitumor effects, which proves this anticancer effect of HPLN is very specific to the target cancer cells and dependent upon drug. No abnormalities in liver and kidney function tests, complete blood counts or pathology of major organs are observed from tail-vein administrations. Theses targeted HPLNs showed much better cytotoxicity over a conventional untargeted PEG-liposomal Doxorubicin formulation (Doxil®). Additionally the targeted HPLN could be found in the tumor cells in a murine model. In conclusion, we have found the safe and efficient targeted HPLN delivery system of anticancer drugs to childhood ALL and Ewing's Sarcoma.
Citation Format: Hyunggyoo Kang, Violette Shahbazian, Amanda Schafenacker, Jon Nagy, Timothy Triche. Development of selective therapy of childhood ALL and Ewing's sarcoma using targeted-hybrid polymerized liposomal nanoparticles (HPLN). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5424. doi:10.1158/1538-7445.AM2014-5424