Metabolite assay of T cells that are antigen-specially activated by viscoelastic synthetic antigen presenting cells

ABSTRACT:

Adoptive T cell receptor (TCR)–based immunotherapy offers a powerful strategy to target solid tumors. However, the physical properties of the antigen-presenting interface regulate T cell metabolic programming remains poorly defined. Here we develop synthetic viscoelastic activating cells (SynVAC), artificial antigen-presenting cells whose stress-relaxation kinetics are chemically tuned independently of stiffness and of peptide–MHC (pMHC) and co-stimulatory ligand density. SynVAC-pMHC provides a defined, scalable platform that outperforms monocyte-derived dendritic cells to enrich antigen-specific CD8+ T cells. Fast-relaxing SynVAC-pMHC amplifies TCR signaling and mTOR activity, drives metabolic remodeling, and programs antigen-specific T cells toward an energetically favorable state with improved memory-like features after expansion. TCR-T cells expanded using fast-relaxing SynVAC-pMHC exhibit superior persistence and durable antitumor activity in melanoma and ovarian cancer models. These results establish cell-mimetic viscoelasticity as a key biophysical cue governing T cell metabolism and differentiation and offer a fully synthetic strategy for manufacturing potent TCR-T cells.

INSTRUMENT(S): Liquid Chromatography MS - alternating - hilic

PROVIDER: MTBLS15444 | MetaboLights | 2026-09-03

REPOSITORIES: MetaboLights