# Identification of cancer neoepitope-specific T cells using novel high-throughput hydrogel based platforms

> **NIH NIH R33** · JOHNS HOPKINS UNIVERSITY · 2024 · $428,438

## Abstract

Abstract
Immunotherapies for cancer, including Adoptive Cell Transfer (ACT), chimeric antigen receptor
(CAR) T cell therapy, and Immune Checkpoint Blockade (ICB), have seen great clinical
success. However, they are still limited by cost, variable efficacy and resistance, and lack of
quality targets. Technologies to track immune responses, and in particular tumor-specific T cell
responses, would help researchers and clinicians to better understand variable responses in
patients, design better targets for therapies, and track patient health outcomes. In this proposal,
we aim to adapt our novel hydrogel-based immune cell expansion system to detect and
characterize rare, neo-epitope specific T cells in the peripheral blood. This platform, termed the
artificial T cell stimulation matrix (aTM), is a hyaluronic acid hydrogel conjugated with signals 1
(peptide-MHC), 2 (anti-CD28) and 3 (cytokine support). In order to create an aTM-based high-
throughput detection system, we will first investigate the effects of physical (i.e. stiffness) and
biochemical (i.e. activation molecules and cytokines) cues of the aTM on the expansion of neo-
epitope specific anti-tumor T cells in mice. We will test the optimized aTM for batched expansion
from bulk murine splenocytes in order to create a high-throughput system. Next, we will develop
a process to detect and expand tumor-associated antigen-specific T cells from peripheral blood
of healthy donors and compare this to current gold standards of antigen-specific T cell
detection. Finally, because disease status may impact our ability to detect rare T cells, we will
verify that the system can be used for detection of neoepitope-specific T cells from the
peripheral blood of melanoma patients. Access to blood from patients will also allow us to
determine how ICB treatment affects the immune response to the tumor by investigation of
expanded neo-epitope specific T cell phenotype and function before and after therapy. The
development of aTM as a high-throughput detection system for neo-epitope, patient-specific T
cell responses will allow pre-clinical and clinical researchers to study immune responses to
cancer and to improve cancer immunotherapies by bringing the power of these therapies to
more patients.

## Key facts

- **NIH application ID:** 10798450
- **Project number:** 1R33CA278429-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** JONATHAN P SCHNECK
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $428,438
- **Award type:** 1
- **Project period:** 2024-02-08 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10798450

## Citation

> US National Institutes of Health, RePORTER application 10798450, Identification of cancer neoepitope-specific T cells using novel high-throughput hydrogel based platforms (1R33CA278429-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10798450. Licensed CC0.

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