# Biomaterials for Targeted Modulation of Conventional Type 1 Dendritic Cells

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2022 · $458,277

## Abstract

SUMMARY
Immunotherapy has shown great promise to cure cancers, especially with the success of checkpoint blockades
and chimeric antigen receptor (CAR) T cell therapies, but its utility is still limited by low patient response rate,
poor efficacy against many solid tumors, and/or severe side effects. These issues motivate the development of
new immunotherapy that can elicit potent and persistent cytotoxic T lymphocyte (CTL) responses and minimize
off-target toxicity. Targeted modulation of type 1 conventional dendritic cells (cDC1s), a subset of DCs superior
in antigen cross-presentation, in lymph nodes will enable optimal activation of CTL responses and result in robust
immunotherapy, but has not been achieved so far. The primary goal of this project is to develop a macroscale
materials-based system that integrates immune cell-homing macroporous materials with metabolic glycan
labeling to achieve cDC1 recruitment, labeling, and targeting in vivo. With this material system, we aim to develop
an unprecedented technology for targeted conjugation of immunomodulatory agents, including antigens,
adjuvants, and cytokines, to cDC1s in lymph nodes, and further develop potent and safe cancer immunotherapy.
To achieve this, an injectable macroporous biomaterial loaded with cDC1-recruiting chemokines and azido-
sugars will be used to recruit and metabolically label cDC1s with chemical tags (e.g., azido group) in situ. These
chemically tagged cDC1s can migrate from the biomaterial to lymph nodes for subsequent targeted conjugation
of immunomodulatory agents via efficient and bioorthogonal click chemistry. Experiments will be organized
around three aims. In Aim 1, injectable pore-forming alginate gels with independently tunable pore size, stiffness,
viscosity, and chemokine release kinetics will be developed, and the impact of each parameter on the immune
cell recruitment profile will be elucidated, in order to rationally design macroporous materials that can
preferentially recruit and metabolically label cDC1s with azido groups in situ. In Aim 2, targeted delivery of tumor
neoantigens and adjuvants or liposomal vaccines to azido-labeled cDC1s in lymph nodes via click chemistry will
be explored, with a goal of improving neoantigen-specific CTL responses and the overall antitumor efficacy
against poorly-immunogenic solid tumors. In Aim 3, targeted conjugation and surface display of
immunomodulatory agents on cDC1s in lymph nodes will be explored to regulate cDC1-T cell interactions and
amplify CTL responses. We hypothesize that cytokines, once conjugated, can be retained on cDC1 surface for
hours to provide continuous stimulation to effector T cells during the T cell priming process. The completion of
this project will lead to new immunotherapies with robust antitumor efficacy against solid tumors and reduced
off-target side effects. Further, the cDC1 recruitment, labeling and targeting technology will also be promising for
future development of therapies again...

## Key facts

- **NIH application ID:** 10522301
- **Project number:** 1R01CA274738-01A1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Hua Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $458,277
- **Award type:** 1
- **Project period:** 2022-09-05 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10522301

## Citation

> US National Institutes of Health, RePORTER application 10522301, Biomaterials for Targeted Modulation of Conventional Type 1 Dendritic Cells (1R01CA274738-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10522301. Licensed CC0.

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