# Development of Bone-Targeting Antibodies for Ewing Sarcoma Using Genetic Code Expansion

> **NIH NIH R21** · RICE UNIVERSITY · 2021 · $225,352

## Abstract

PROJECT SUMMARY/ABSTRACT
Ewing sarcoma (ES) is the second most common pediatric bone cancer with peak incidence during the
adolescent and young adult period. ES is an extremely aggressive malignancy with the current treatment
regimen relying on a combinatorial approach of chemotherapy, radiotherapy, and/or surgery. 65%-75% of ES
patients can be cured with the current treatment strategies, but at a risk of suffering signficant systemic side
effects. These include high risks for infection secondary to immunosuppression from cytotoxic chemotherapy to
long term effects that can lead to serious cardiac, learning deficits, reproductive capabilities and even second
malignancies. Therefore, it is essential to develop more precise, effective therapeutic approaches to maximize
patient outcomes while minimizing devastating side effects. Our long-term goals are to design new therapeutic
strategies against bone cancer cells through a synergistic collaborative effort between labs at Rice University
and the Baylor College of Medicine. The overall goal of this proposal is to develop bone-targeting precision
therapeutic biologics for the treatment of ES. To achieve this goal, the first research direction will focus on the
generation of bone-targeting antibodies for ES using an innovative genetic code expansion technology we have
recently pioneered. Bisphosphonates are a class of negatively charged molecules able to selectively bind to
mineralized, positively charged bone matrix. Site-specific conjugation of bisphosphonates to antibodies will
deliver a high concentration of therapeutic antibodies to the bone and activated within the acidic tumor
microenvironment for better therapeutic efficacy and reduce adverse side effects associated with systemic
delivery. To demonstrate the enhanced therapeutic profile of these bone-targeting antibodies for the treatment
of ES, we will study their effects on the survival and progression of ES using ES cells or patient-derived xenograft-
derived primary ES cells. Our efforts in this project will yield a collection of bone-targeting antibodies and
demonstrate their enhanced therapeutic profile on Ewing sarcoma. Considering the growing success of antibody
therapy in the clinic, selective delivery of therapeutic antibodies to the bone microenvironment will provide a
promising avenue for different bone-associated primary and metastatic malignancies.

## Key facts

- **NIH application ID:** 10111649
- **Project number:** 1R21CA255894-01
- **Recipient organization:** RICE UNIVERSITY
- **Principal Investigator:** Han Xiao
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $225,352
- **Award type:** 1
- **Project period:** 2021-04-05 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10111649

## Citation

> US National Institutes of Health, RePORTER application 10111649, Development of Bone-Targeting Antibodies for Ewing Sarcoma Using Genetic Code Expansion (1R21CA255894-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10111649. Licensed CC0.

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