# Development of an engineered CCL20 as a therapeutic molecule for chronic graft-versus-host disease

> **NIH NIH R43** · XLOCK BIOSCIENCES, LLC · 2022 · $259,613

## Abstract

Project Summary/Abstract
The goal of this project is to validate a novel therapeutic lead compound for the treatment of chronic graft
versus host disease (cGVHD). Chronic graft versus host disease (cGVHD), the leading cause of long-term
morbidity and mortality following allogeneic hematopoietic stem cell transplantation, affects up to 25,000 new
patients each year in the U.S. It is now widely accepted that dysregulated T helper 17 (Th17) cells contribute to
the development and progression of cGVHD, which can damage virtually any organ system. Up to 40% of
cGVHD patients die within seven years during treatment and half of cGVHD patients become unresponsive to
corticosteroid therapy with few alternatives. This dismal clinical outlook highlights a clear unmet need for a
safe and effective treatment for cGVHD. Chemokines orchestrate the migration of inflammatory cells during
normal immune function and are required for proper organ development and homeostasis. When aberrant
chemokine function occurs, improper recruitment of immune cells can lead to a variety of inflammatory
pathologies with devastating effects on a patient’s quality of life. The chemokine CCL20 and its G protein-
coupled receptor CCR6 drive the continuous recruitment of Th17 cells in several autoimmune and chronic
inflammatory diseases (e.g. psoriasis, psoriatic arthritis and rheumatoid arthritis) and are likely to participate in
the pathogenesis of cGVHD. Our published biochemical, cell-based and in vivo studies prove that an
engineered dimeric form of CCL20 molecule (CCL20LD) completely reverses its normal pro-inflammatory
functional profile. This lead molecule was therapeutically efficacious in mouse models of psoriasis and psoriatic
arthritis and has the potential to treat other Th17-mediated diseases. We propose to validate CCL20LD as a
next-generation biologic treatment for cGVHD. In Aim 1, XLock Biosciences and its academic collaborators at
City of Hope will test the therapeutic efficacy of the engineered protein in an established murine model of
cGVHD with an Aim 1 milestone to show statistically significant reductions in multiple disease signs as
compared to control animals. In Aim 2, our company will produce a 2nd–generation XTEN extended version of
CCL20LD that maintains the in vitro inhibition of cell migration at levels comparable to the 1st–generation
molecule. Successful completion of Aim 2 milestones will result in at least two version of CCL20LD with
varying lengths of XTEN sequence that preserve the inhibitory potency of CCL20LD and prolong its circulating
lifeteim in vivo. Altering CCR6 signaling through the engineering of its native ligand is an innovative paradigm
shift in clinical approaches for treating auto-inflammatory diseases. Validation of engineered CCL20 variants
as biological therapeutic for cGVHD will have significant positive impact for patients by reducing side effects
associated with prolonged administration of prednisone, the standard treatment for ...

## Key facts

- **NIH application ID:** 10485836
- **Project number:** 1R43HL164271-01
- **Recipient organization:** XLOCK BIOSCIENCES, LLC
- **Principal Investigator:** William R Clarke
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $259,613
- **Award type:** 1
- **Project period:** 2022-06-15 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10485836

## Citation

> US National Institutes of Health, RePORTER application 10485836, Development of an engineered CCL20 as a therapeutic molecule for chronic graft-versus-host disease (1R43HL164271-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10485836. Licensed CC0.

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