Abstract 1708: Nanofluidic drug-eluting seed for sustained intratumoral immunotherapy in triple negative breast cancer

Abstract

Abstract Conventional systemic immunotherapy administration often results in insufficient anti-tumor immune response and adverse side effects. Delivering immunotherapeutics intratumorally could maximize tumor exposure, elicit robust anti-tumor immune response, and minimize toxicity. To fulfill the unmet clinical need for sustained local drug delivery and to avoid repeated intratumoral injections, we developed a nanofluidic-based device for intratumoral drug delivery called the nanofluidic drug-eluting seed (NDES). The NDES is inserted intratumorally using a minimally invasive trocar method similar to brachytherapy seed insertion and offers a clinical advantage of intratumoral drug elution. Drug diffusion from the NDES is regulated by physical and electrostatic nanoconfinement, thereby resulting in constant and sustained immunotherapeutic delivery without the need for repeated injections or clinician intervention. In this study, the NDES was utilized to deliver immunotherapeutics intratumorally in the 4T1 orthotopic murine mammary carcinoma model, which recapitulates triple negative breast cancer. We demonstrated that NDES-mediated intratumoral release of agonist immunotherapeutic monoclonal antibodies, OX40 and CD40, resulted in potentiation of local and systemic anti-tumor immune response and significant inhibition of tumor growth compared to control mice. Further, mice treated with NDES-CD40 demonstrated minimal liver damage compared to systemically treated mice. Collectively, our study highlights the NDES as an effective platform for sustained intratumoral immunotherapeutic delivery. The potential clinical impact is tremendous given that the NDES is applicable to a broad spectrum of drugs and solid tumors. Citation Format: Corrine Ying Xuan Chua, Priya Jain, Marco Folci, Andrea Ballerini, Jessica Rhudy, April Gilbert, Shail Shaibala, Giacomo Bruno, Carly S. Filgueira, Cassian Yee, E. Brian Butler, Alessandro Grattoni. Nanofluidic drug-eluting seed for sustained intratumoral immunotherapy in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1708.