# Removing sialic acid ligands of CD28 to enhance T cell cancer immunotherapy

> **NIH NIH R21** · SCRIPPS RESEARCH INSTITUTE, THE · 2023 · $226,250

## Abstract

Summary
T cells play a central role in the adaptive immune system and are activated in response to T cell receptor (TCR)
recognition of antigen loaded on the major-histocompatibility complex (MHC) of antigen presenting cells
(APCs). In order to fully achieve T cell effector function, an essential “second signal” is provided by engagement
of the T cell costimulatory receptor CD28 with its B7 ligands (CD80/CD86) on the APC. We recently
demonstrated that sialic acids on T cells and APCs dampen CD28 binding to CD80/CD86 and that removal of
sialic acids with sialidase enhances T cell proliferation. Sialic acid removal is also synergistic with programmed
cell death protein-1 (αPD1) checkpoint inhibitor blockade for functional revival of exhausted T cells. In this
project, we will develop bifunctional αPD1-sialidase conjugates that are expected to combine the benefits of
PD1 blockade with removal of sialic acid ligands of CD28 to promote engagement with B7 ligands and enhance
T cell activation. We will evaluate these reagents in animal models of cancer for their therapeutic potential to
invigorate exhausted T cells and suppress cancer progression.

## Key facts

- **NIH application ID:** 10668007
- **Project number:** 1R21AI171628-01A1
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** JAMES C PAULSON
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $226,250
- **Award type:** 1
- **Project period:** 2023-02-17 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10668007

## Citation

> US National Institutes of Health, RePORTER application 10668007, Removing sialic acid ligands of CD28 to enhance T cell cancer immunotherapy (1R21AI171628-01A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10668007. Licensed CC0.

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