Topo-engineered OMVs as a Multi-functional Platform to Promote Antitumor Immunity via Enhanced Antigen Presentation and T Cell Costimulation

• Grant number: 25/11818-1
• Support Opportunities: Regular Research Grants
• Start date: January 01, 2026
• End date: December 31, 2028
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Marcio Chaim Bajgelman
• Grantee: Marcio Chaim Bajgelman
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Campinas , SP, Brazil
• City of the host institution: Campinas

Abstract

Personalized polypeptide vaccines provide a great opportunity to treat tumors with high mutation rates. However, the current strategy for constructing polypeptide vaccines mainly relies on the physical mixture of adjuvants and polypeptides, leading to inefficient antigen presentation and poor patient compliance. Outer membrane vesicles (OMVs), derived from bacterial cells, can be easily engineered to carry molecules of interest, garnering increasing attention as a potent and versatile vaccine platform. In this collaborative project between the faculty of Health Sciences at the University of Macau and the Brazilian National Center for Research in Energy and Materials, we propose an innovative approach based on topo-engineered OMVs for efficient antigen presentation and rapid antigen loading. In specific, OMVs with self-adjuvanting properties serving as nanocarriers are first modified with a T cell costimulator ligand and further inserted with maleimide-conjugated polymer on the surface for antigen loading. Then, the tumor-specific polypeptides containing cysteine are synthesized and loaded onto OMVs via click reaction, generating biomimetic spike topology on OMVs. As a result, the nano-spike topological structure facilitates the lysosomal escape of polypeptides after uptake by dendritic cells (DCs). With the help of costimulators, the nanovaccine can not only promote antigen presentation but also promote T cell activation, resulting in enhanced anticancer immunity. Moreover, modular "plug-and-play" antigen conjugation technology enables flexible pan-cancer neoantigen loading with high density and rapid production, meeting urgent clinical needs. This engineered biomimetic topological nanovaccine exhibits promising antitumor efficacy, accelerating the clinical translation of personalized tumor vaccines. (AU)