# Engineered immunotherapies neutralizing interleukin-22 binding protein

> **NIH NIH R21** · DUKE UNIVERSITY · 2022 · $197,394

## Abstract

Inflammatory bowel diseases, including ulcerative colitis and Crohn's disease, are commonly treated with
monoclonal antibodies against inflammatory cytokines. However, a large proportion of patients do not
respond to such biologics or experience diminishing efficacy over time. Additionally, episodic dosing can
exacerbate the production of anti-drug antibodies. Even in responding patients, while anti-cytokine
therapies can ameliorate disease symptoms, they often fail to induce adequate intestinal epithelial
regeneration. There is therefore a critical unmet need for an alternative therapy for inflammatory bowel
disease that generates predictable therapeutic efficacy for broad patient populations by both reducing
inflammation and promoting tissue regeneration. Active Immunotherapy, where anti-inflammatory immune
responses are generated within the patient using engineered immunogens, is an alternative but nascent
strategy that may offer improved therapeutic efficacy. This project aims to design an active immunotherapy
against a key mediator of inflammatory bowel disease, IL-22 binding protein (IL-22BP). The cytokine it
inhibits, IL-22, is a member of the IL-10 family and plays a central role in regulating the intestinal barrier in
healthy tissue and during epithelial regeneration; thus, neutralizing IL-22BP promises to facilitate the pro-
regenerative properties of IL-22 for the amelioration of IBD. Active immunotherapies will be designed using
innovative supramolecular nanomaterials designed to contain precise quantities of B-cell epitopes raising
neutralizing responses against IL-22BP and TNF, along with exogenous T-cell epitopes designed to
provide CD4+ T cell help without breaking T-cell tolerance to the native cytokines. Efficacy will be assessed
in a murine model of dextran sodium sulfate-induced colitis. If successful, this high risk/high reward project
will establish a-proof-of-concept for combinatorial active immunotherapies that are both anti-inflammatory
and regenerative in the context of IBD, constituting a first demonstration of this strategy that could have
broader application to other inflammatory diseases and cytokines.

## Key facts

- **NIH application ID:** 10538770
- **Project number:** 1R21EB033687-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Joel H Collier
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $197,394
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10538770

## Citation

> US National Institutes of Health, RePORTER application 10538770, Engineered immunotherapies neutralizing interleukin-22 binding protein (1R21EB033687-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10538770. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*