# Biomimetic Matrix for Ex Vivo and In Vivo Activation of T Cells

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $479,444

## Abstract

PROJECT SUMMARY
 The objective of this study is to engineer an artificial T cell-stimulating matrix (aTM) that presents antigen-specific
and cell-specific biochemical and biophysical cues to control phenotype and improve functional profiles of T cells in a
biomimetic context that captures key biochemical and biophysical features of the lymph node (LN). LN provides the
critical microenvironment that orchestrates the presentation format and dynamics of the antigen-specific signals in a
precise and controlled manner that leads to T cell activation, expansion, and maturation. Currently available T cell
stimulating matrices while carrying the antigen-presentation complexes and co-stimulating cues, however, lacks
adequate supporting cues inherent to the T cell stimulating microenvironment in the LN. We will design and
characterize an aTM that integrates the three key T-cell stimulating signals: antigen-specific (Signal 1), co-stimulatory
(Signal 2), and cytokines (Signal 3), together with extracellular matrix (ECM) molecules and tunable biophysical
properties inspired by the properties of both antigen-presenting cells (APCs) and the LN. We will test the hypothesis
that co-presenting the APC signal cues in such a biomimetic context during T cell stimulation will result in functional
T cells with controlled phenotypic profiles and potency. and mechanism revealing how all signaling cues synergize to
active and polarize T cells. In Specific Aim 1, we will determine key matrix properties of the aTM that mediate robust
CD8+ T cell activation using aTMs prepared from hyaluronic acid (HA) hydrogel and HA-nanofiber composite (NHC)
matrix. In Specific Aim 2, we will define optimal signaling cues and their presentation configuration that influence
CD4+ T cell activation and polarization on aTM; and demonstrate persistence and functions of aTM-stimulated and
adoptively transferred antigen-specific CD4+ T cells. In Specific Aim 3, we will use aTM microparticles to co-stimulate
CD8+ and CD4+ T cells and evaluate therapeutic benefits of a combination treatment with CD4+ and CD8+ T cells in
a cancer immunotherapy mouse model. If successful, this study will result in the first set of engineered aTM that
delivers robust stimulation of antigen-specific CD8+ and CD4+ T cells that promise improved therapeutic outcomes;
and further enrich our understandings of design principles and mechanism of signaling cues in stimulation, polarization,
and activation of T cells.

## Key facts

- **NIH application ID:** 10072818
- **Project number:** 1R01EB029341-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Hai-Quan Mao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $479,444
- **Award type:** 1
- **Project period:** 2020-07-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10072818

## Citation

> US National Institutes of Health, RePORTER application 10072818, Biomimetic Matrix for Ex Vivo and In Vivo Activation of T Cells (1R01EB029341-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10072818. Licensed CC0.

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