Abstract 1074: Programmable bacteria induce durable tumor regression and systemic antitumor immunity

Abstract

Abstract Synthetic biology is driving a new era of medicine through the engineering of living cells. This transformative approach allows for the creation of systems that intelligently sense and respond to diverse environments, adding specificity and efficacy beyond the capabilities of molecular-based therapeutics. One particular area of focus has been the engineering of bacteria as therapeutic delivery systems to selectively release therapeutic payloads in vivo. We recently engineered a non-pathogenic Escherichia coli strain to specifically lyse within the tumor microenvironment and release an encoded nanobody antagonist of CD47 (CD47nb), an anti-phagocytic receptor that is commonly overexpressed in several human cancer types. We show that delivery of CD47nb by tumor-colonizing bacteria increases activation of tumor-infiltrating T cells, stimulates rapid tumor regression, prevents metastasis and leads to long-term survival in a syngeneic tumor model in mice. Moreover, we report that local injection of CD47nb-expressing bacteria stimulates systemic tumor-antigen-specific immune responses that reduce the growth of untreated tumors, providing proof-of-concept for an abscopal effect induced by an engineered bacterial immunotherapy. We have expanded this approach to include additional human and murine specific immunotherapeutic payloads and evaluate efficacy in multiple tumor model systems. Citation Format: Sreyan Chowdhury, Kelly Pu, Clare Nimura, Samuel Castro, Courtney Coker, Taylor Hinchliffe, Nicholas Arpaia, Tal Danino. Programmable bacteria induce durable tumor regression and systemic antitumor immunity [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1074.