Abstract 3902: The Nanoprimer: A significant opportunity to boost the efficacy of cancer therapies
Authors: Devallière Julie , Poul Laurence , Bergère Maxime , Mpambani Francis , Darmon Audrey , Jibault Océane , Germain Matthieu 
Published: March 2024

Abstract
Nanomedicines are among the most promising novel delivery systems and are highly promising as therapeutic agents in oncology. However, their use is still limited by nanoparticle hepatic clearance which is responsible for low delivery to the target site. Moreover, the unintended liver distribution could cause harmful side effects. Curadigm’s innovative Nanoprimer technology aims to shift the balance of therapeutics bioavailability and toxicity. The platform is designed to decrease nanomedicines' liver trapping and increase their systemic bioavailability for optimal accumulation in target tissues. This technology can redefine the benefit/risk ratio of therapeutics, improving their clinical outcomes and treatment value. The Nanoprimer is an engineered, biocompatible liposome that transiently and specifically occupies the cells of the mononuclear phagocytic system responsible for sub-optimal therapeutics bioavailability. The Nanoprimer is administered just before the therapeutic, temporarily reducing drug clearance and elimination. Proofs-of-concept were realized by combining the Nanoprimer with different therapeutic agents such as irinotecan-loaded liposomes and nucleic acid-loaded lipid nanoparticles (LNP). One example is a study conducted in collaboration with the Langer Lab at MIT that shows that the Nanoprimer increases mRNA- and siRNA-based therapeutics efficiency by 32% and 49% respectively. Efficacy studies in a triple-negative breast cancer mouse model reveal that the Nanoprimer increases by 2-fold the anti-tumor efficacy of siRNA LNP therapy. Data demonstrate the safety of the Nanoprimer, along with its ability to maximize the inhibition of primary tumor growth and pulmonary metastasis by systemic siRNA LNP treatment. In a collaborative study with the NCL*, the Nanoprimer was shown to stimulate the immune response in a systemic vaccine model using ovalbumin-coated gold nanoparticles (GNP-OVA). Administration of the Nanoprimer before immunization of mice by intravenous injection of GNP-OVA, results in a dramatic increase in anti-OVA antibody levels with IgGs detected as early as 7 days. Furthermore, IgG and IgM antibodies remain elevated at day 28 showing a robust and sustainable immune response. Nanoprimer ability to enhance immune response shows its great potential in immunotherapy, especially for cancer vaccines. Altogether, these data demonstrate that the ubiquitous nature of the Nanoprimer mode of action allows its application to a broad spectrum of therapeutics, from nucleic acid-loaded LNP to immunotherapy. Efficacy studies conducted in mouse models highlight the potential for the Nanoprimer to empower nanotechnology for oncology treatments. *We acknowledge NCL, Frederick National Laboratory for Cancer Research sponsored by the NCI for the help with conducting these experiments.
Citation Format: Julie Devallière, Laurence Poul, Maxime Bergère, Francis Mpambani, Audrey Darmon, Océane Jibault, Matthieu Germain. The Nanoprimer: A significant opportunity to boost the efficacy of cancer therapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3902.