Oral Presentation Asia-Pacific Vaccine and Immunotherapy Congress 2026

A programmable CAR T platform for viral sensing and customizable antiviral intervention (#55)

Yidan Wang 1 2 , Linfa Wang 2 , Haifeng Ye 1
  1. School of Life Sciences, East China Normal University, Shanghai, China
  2. EID, Duke-NUS medical school, Singapore, SINGAPORE

The relentless evolution of coronaviruses, including SARS-CoV-2 and its related lineages, continues to erode the efficacy of existing antiviral and immune interventions, underscoring the urgent need for adaptable strategies capable of responding to antigenic drift and viral diversification. Here, we develop a modular and programmable chimeric antigen receptor (CAR) T cell platform, PVARC-CAR (programmable viral antigen recognition and clearance CAR), designed to couple pathogen sensing with tailored antiviral effector responses. We first engineered a heterodimeric receptor (PVARC-CARHet) combining CR3022 and S309 single-chain variable fragments (scFvs), enabling potent T cell activation by soluble spike, pseudotyped and authentic sarbecoviruses, and virus-infected cells. To directly link pathogen sensing to antiviral intervention, we engineered PVARC-CARNAb T cells that secrete neutralizing antibodies (NAbs) in an antigen-inducible and dose-tunable manner. We further established a universal adaptor-based design (PVARC-CARUniv) in which exchangeable bispecific adaptors allow rapid, on-demand redirection to evolving viral antigens. In a mouse model mimicking SARS-CoV-2 infection, PVARC-CARUnivNAb T cells combined targeted cytotoxicity with localized NAb production, resulting in efficient clearance of infected cells and markedly improved survival. Together, the PVARC-CAR platform provides a versatile strategy for real-time viral surveillance and programmable antiviral intervention, offering a broadly applicable approach to countering rapidly evolving viral threats.