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bioRxiv · 10.1101/2025.06.24.661128

Functionalizing hydrogel nanovials with vesicles mimicking antigen-presenting vesicles and cancer exosomes improves T cell capture and activation

Olson, B. A.·Mellody, M. P.·Soemardy, C.·Mao, Z.·Mei, A.·Lippert, K.·Hoffmann, M. A. G.·Di Carlo, D.·Mayo, S. L.
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Abstract

Recent advances have demonstrated the application of microcavity-containing hydrogel microparticles, known as nanovials, for the massively parallel and high-throughput screening of therapeutic T cell populations for adoptive cell therapies. Nanovial cavities coated with peptide-MHC (pMHC) or antigen tetramers selectively bind to their cognate T cell receptor (TCR) or chimeric antigen receptor (CAR) to activate T cells and capture secreted cytokines. However, binding of tetramers or recombinantly expressed antigen by T cells is not always correlated with T cell activation or cytotoxicity as the binding interface is not fully representative of the natural immunological synapse formed between T cells and professional antigen-presenting cells (APCs). Here, we leverage the recent discovery of an ESCRT- and ALIX-binding region (EABR) sequence to generate antigen-presenting vesicles and cancer-mimicking exosomes from standard HEK293T and Expi293F cell cultures. EABR-mediated vesicles present natural, full-length oncologically-relevant membrane proteins embedded in lipid bilayers to functionalize the nanovial cavity with cell-like membranes. These hydrogel nanovials functionalized with the EABR-mediated vesicles show improved T cell capture of 1G4 T cells and enhanced activation of HER2 CAR-T cells compared to hydrogel surfaces functionalized with recombinantly-expressed soluble proteins.

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Olson, B. A., Mellody, M. P., Soemardy, C., Mao, Z., Mei, A., Lippert, K., Hoffmann, M. A. G., Di Carlo, D., Mayo, S. L.. 2025-06-27. Functionalizing hydrogel nanovials with vesicles mimicking antigen-presenting vesicles and cancer exosomes improves T cell capture and activation. https://doi.org/10.1101/2025.06.24.661128

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