# Engineer Immune Cells via Chemoenzymatic Glycan Editing

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 2023 · $944,319

## Abstract

PROJECT SUMMARY/ABSTRACT
 Cell-cell interactions are involved in numerous biological processes, including immune responses,
embryonic development, neuronal signaling and cancer metastasis. Some major gaps in our understanding of
cell-cell interactions include: what are the interacting partners of a specific cell type at different stages of a
biological process? How to modify the cell-surface landscape of these interacting partners to tune the functions
of a specific cell type with minimum perturbation of its endogenous functions?
 The objective of this project is to develop glycosyltransferase-based chemoenzymatic methods to
incorporate biopolymers, including enzymes and monoclonal antibodies, onto the cell surface to study these
puzzles.
 In Aim 1 of this project, we will identify or engineer a promiscuous glycosyltransferase that can transfer
biopolymer-functionalized unnatural sugars from the corresponding nucleotide sugar donors to the cell-surface
glycocalyx of the cells of interest. When the bioploymer is an enzyme, it will enable the proximity-dependent
labeling of prey cells that interact with the cells of interest (bait cells) that harbor the enzyme, providing that the
cell surface of prey cells expresses the substrates to be modified by the enzyme. Subsequently, the signal
generated by the labeling can be detected and analyzed ex vivo by flow cytometry. In Aim 1d and Aim 2, we
will apply this method to probe cell-cell interactions in vivo using mouse models. The focus will be the
identification of interacting partners of specific immune cell types during immune activation and T-cell
exhaustion (T-cell exhaustion is the process during which T cells progressively lose their functions). Finally, we
will develop a method in Aim 3 to conjugate monoclonal antibodies onto immune cells to endow them with
specific targeting capabilities. The migration and anti-tumor efficacy of the modified cells will be evaluated in
mouse tumor models.

## Key facts

- **NIH application ID:** 10578671
- **Project number:** 5R01AI143884-05
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** John Ross Teijaro
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $944,319
- **Award type:** 5
- **Project period:** 2019-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10578671

## Citation

> US National Institutes of Health, RePORTER application 10578671, Engineer Immune Cells via Chemoenzymatic Glycan Editing (5R01AI143884-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10578671. Licensed CC0.

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