Abstract 312: Targeted NanoSpheres (TNS)

Abstract The tumor-targeted, nanoparticle delivery technology has shown the possibility of increasing the delivered dose of virtually any small therapeutics to tumor cells while limiting the drug uptake by normal tissues, thereby greatly increasing the effective MTD. By refining the early formulations and after extensive testing, we developed a novel targeted liposomal nanoparticle, Targeted NanoSpheres (TNS). We showed this novel nano-formulated platform can overcome many deficiencies of conventional nanoparticles and therefore has enhanced potential as an effective delivery vehicle for virtually any type of cancer for which a suitable tumor cell surface antigen is present. We have developedNV103, a first-in-class anti-CD99 TNS (CD99-TNS/Irinotecan), for the treatment of Ewing Sarcoma (EWS), a highly lethal pediatric and young adult bone and soft tissue tumor driven by a fusion protein, typically EWS/FLI1 in over 85% of cases. Cancer cells have the ability to develop resistance to the chemotherapy. Our present salvage/rescue study with NV103 showed that NV103 can overcome irinotecan resistance of Ewing tumor with simple change of dose schedule (dose intensification), not increasing the dose. The results from our salvage/rescue studies with NV103 suggested that successful dose intensification schedules with NV103 could be used to treat relapsed or resistant patients in future clinical trials. Furthermore, Targeted Nanosphere (TNS) can be used to overcome drug resistance of various cancers.This platform is also being investigated for other types of cancer that either express CD99, or other tumor antigens like GD2 and B7-H3. Citation Format: HyungGyoo Kang, Jon Nagy, Bryon Upton, Racheal Upton, Timothy Triche, Timothy Triche. Targeted NanoSpheres (TNS) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 312.