Engineered microbial antigen-presenting system for targeted T cell activation

Background

Targeted immunotherapy depends on the ability to modulate specific T cell populations to fight chronic infections, cancers, and autoimmune diseases. Achieving precise control over T cell activation is essential for generating effective immune responses while minimizing off-target effects. Traditional vaccines and existing antigen-presenting cell (APC) technologies often fall short of this goal. Conventional vaccines rely on indirect and variable antigen presentation, while synthetic APCs involve complex manufacturing that limits their scalability and clinical use. Attempts to deliver activation components like single-chain MHC molecules through DNA plasmids have largely failed due to inefficiency, leaving a significant gap in the ability to reliably activate T cells in a targeted and controllable manner.

Technology overview

This microbial system serves as a living artificial antigen-presenting platform engineered to display peptide-loaded major histocompatibility complex (MHC) molecules, either class I or class II, on its surface. These modified microbes directly engage T cell receptors and can be further engineered to express the CD80 ectodomain for co-stimulatory signaling and to secrete cytokines that enhance T cell activation. The displayed peptide antigen can be customized to selectively stimulate specific T cell populations. This direct interaction enables precise immune targeting for therapeutic applications in cancer, infectious disease, and autoimmune conditions. The system can also be used as a tool to identify antigen-specific T cells, offering potential for both therapy and diagnostics.