# Localization of Antibody Drugs to Arthritic Joints via Collagen Hybridization

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $402,086

## Abstract

PROJECT SUMMARY (PI: YU)
Since bones and cartilage (B&C) are common sites of serious degenerative diseases (e.g. cancer, arthritis,
osteoporosis), a strategy to localize therapeutic agents to skeletal tissue (for high efficacy) with minimal
distribution to other sites (for low side effects) could lead to significant improvement in treating a wide range of
debilitating conditions. Recent advances in antibody therapy have produced promising drugs for rheumatoid
arthritis (e.g. infliximab, abatacept); however they have off-site, target related side effects due to systemic
immune suppression. Due to these side effects, mainly serious infection, patients need to be screened for
therapy, and co- or concurrent administration of two types of immune modulatory drugs is not practiced
although such approach may treat RA symptoms better. Based on a new understanding of RA biology and our
recent findings that collagen hybridizing peptide (CHP) can bind to degraded collagen in skeletal tissues
undergoing pathologic resorption, we propose to develop joint targeted antibody therapy that can seek and
bind to collagens degraded by rheumatoid arthritis (RA). In aim 1, we will synthesize new CHP structures that
have high affinity to denatured collagen. In aim 2, we plan to develop RA joint-targeted anti-TNF-a therapy by
conjugating CHP to Fab that can neutralize mouse TNF-a. In aim 3, we will study the pharmacological
properties, efficacy, and systemic immune suppression of the Fab-CHP conjugates in RA mouse models.
Latest understanding of RA disease mechanism teaches that immune activations in RA take place locally at the
disease site and most of TNF-a are produced by the inflamed tissue. Since off-site side effects are the major
limitation of antibody therapy, the ability to localize immunomodulatory drugs could lead to high efficacy and
low side effects. The success of this work may lead to an entirely new platform for antibody therapy for RA and
other autoimmune diseases.

## Key facts

- **NIH application ID:** 10973074
- **Project number:** 1R01AR084689-01
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Michael S Yu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $402,086
- **Award type:** 1
- **Project period:** 2024-08-22 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10973074

## Citation

> US National Institutes of Health, RePORTER application 10973074, Localization of Antibody Drugs to Arthritic Joints via Collagen Hybridization (1R01AR084689-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10973074. Licensed CC0.

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