Antigen specific scaffold for stimulation and expansion of T-cells 9132

Abstract Description TCR-T cell therapy uses T-cells engineered with receptors that bind to specific MHCp on tumor cells, activating the T cell to kill the tumor. However, activating T cells through the TCR alone is insufficient and requires co-stimulation for a strong anti-tumor response.. In vitro assays are needed to evaluate the potency of engineered T cells, as current assays based on cell-cell interactions are laborious and hard to standardize. We have developed an analytical tool to stimulate and expand engineered T cells. MHCp monomers and CD28 co-engager molecules were attached to an artificial scaffold, creating reagents mimicking professional antigen-presenting cells by engaging both TCR and CD28 on T cells. These PAX reagents were used to activate antigen-specific T cells, with surface markers, cytokine secretion, and cell expansion as readouts. PAX reagents displaying MHCp/a-CD28 successfully stimulated specific T cells, causing: Upregulation of activation markers (CD69, CD137) Increased cytokine production (INF-gamma, TNF-alpha) T cell expansion (up to 30-fold in 1 week). The expanded cells were not exhausted. No activation occurred with PAX reagents displaying negative control MHCp. PAX technology effectively stimulates, activates, and expands antigen-specific T cells ex vivo. This method is highly specific and can be used to: Assess potency of engineered T cells Generate expanded antigen-specific T cell lines Enrich rare T cell populations. Topic Categories Technological Innovations in Immunology (TECH)