Abstract 1581: Nammisomes: Preclinical validation of a platform for selective and synchronized delivery of novel immunotherapy prodrug combinations to tumors

Abstract

Abstract The approval of checkpoint inhibitors, CAR-T cell therapies, and other immunotherapies has led to a significant improvement in cancer patient survival rates over the past 7 years. However, the pace of improvement has slowed lately as the field moves beyond the minority of patients with immune primed or accessible cancers. It is generally expected that rationale combinations of immunotherapies that provide mechanisms to both induce as well as maintain the immune responses in the face of tumor-derived immune checkpoint mediators, will be required to effectively treat these patients. Systemic exposure to such combinations often can give rise to severe toxicity profiles that limit their therapeutic efficacy. Nammisomes are an innovative and unique platform designed to deliver novel immune modulating prodrugs more selectively and synchronously to the tumor site. The immune active agents are conjugated to lipids to create prodrugs that self-assemble into a liposomal bilayer. By mixing multiple prodrugs at the desired ratio, co-formulations are produced with the optimum stoichiometry. These Nammisomes are iv injected and selectively enter tumors through the leaky vasculature within tumors, while remaining in circulation in normal tissues with intact blood vessels, The enriched phagocytic activity in tumor environments causes the release of the active agents within tumors relative to normal tissues limiting systemic exposure and toxicities. Preclinical efficacy and safety data of Nammisomes delivering combinations of a TLR agonist and a checkpoint inhibitor showing anti-tumor efficacy and tolerability in syngeneic mouse models will be presented. In summary, Nammisomes will be highlighted as a combination therapeutic modality to demonstrate the potential of this approach in anti-cancer therapy. Citation Format: David R. Stover, Dhruba Bharali, Tahmineh Safaie, Bruce A. Hay, Rajesh K. Sharma, Scott Ayers. Nammisomes: Preclinical validation of a platform for selective and synchronized delivery of novel immunotherapy prodrug combinations to tumors [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 1581.