Abstract 6747: Engineering M13 filamentous phages to target dendritic cells and elicit anti-tumor immunity

Abstract

Abstract Filamentous phage is a safe and effective vaccine vector that can elicit robust immune responses by activating Toll-like receptor pathways. However, engineering neoantigen-displaying phages for cancer vaccines using phage display technology has been challenging and yielded inconsistent results. We developed a dendritic cell (DC)-targeting cancer vaccine platform with M13 filamentous phages using the phage display technology. The engineered phages express DC-targeting peptides (SLS) on p3 sites and spy-catcher proteins on p8 positions, allowing neoantigens and proteins of interest to be linked to the phage vector. We named our platform SCP (SLS-spy catcher phage). Imaging and western blot showed that spy-tagged proteins can be easily attached to SCP by simple mixing. Further studies demonstrated that targeting DCs can enhance antigen presentation and anti-cancer immunity. We tested SCP in MB49 and B16 mouse models and the serum, spleen and tumor tissues were isolated for further investigation of immune response upon treatment. We found that SCP effectively suppressed tumor growth by inducing systemic anti-tumor humoral and cell-mediated immunity. SCP also showed efficacy in late-stage tumor models. SCP treatment triggered particularly robust local anti-tumor response. Histological and flow cytometry analysis revealed increased infiltration of innate and adaptive immune cells, reduced PDL1 expression, and restricted neovascularization in the tumor microenvironment after intratumoral administration of SCP. Our study demonstrated that SCP can induce multifactorial modifications in the tumor microenvironment to impede tumor growth. SCP overcomes the limitations of traditional phage display technology, enabling a wide variety of peptides and proteins to be loaded onto the phage vectors. SCP is also cost-effective and scalable as phage production and purification processes are relatively mature. We propose that SCP can serve as a universal platform for cancer immunotherapy, and may offer novel treatment options for patients. Citation Format: Yee Man Betty Au-Yeung, Zheng Zeng, Jiandong Huang. Engineering M13 filamentous phages to target dendritic cells and elicit anti-tumor immunity [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 6747.