# LGR5 antibody drug conjugate for the treatment of neuroblastoma

> **NIH NIH R21** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2022 · $182,325

## Abstract

Neuroblastoma (NB) is a cancer of the nervous system outside the brain that occurs in children under 15 years
of age. It is the most frequently diagnosed cancer during infancy, accounting for ~12% of all-cancer related
death in children. It is considered a rare cancer since its overall incidence is significantly less than 6 per
100,000 people in the U.S. Approximately half of NB cases are cured with minimal and sometimes no
chemotherapy while the other half are high-risk patients who only have a long-term survival of ~50% despite
intensive multimodal treatment that is quite toxic.
Antibody–drug conjugates (ADCs) are monoclonal antibodies (mAbs) that are covalently linked to cell-killing
cytotoxins to deliver the payloads into cancers cells. Multiple ADCs have now been approved by FDA for
cancer treatment, including leukemia, breast cancer, and bladder cancer. LGR5 (leucine-rich repeat containing,
G protein-coupled receptor 5) is a membrane receptor that is associated with formation and metastasis of
cancers in the gastrointestinal system. Therapeutic agents targeting LGR5 and its associated pathway are being
developed for gastrointestinal cancers driven by this mechanism. Remarkably, high levels of LGR5 are found
in NB tumor cells, and more LGR5 expression is correlated with poor survival. However, whether LGR5 can
also be targeted for the treatment of high-risk NBs remains unknown.
We have found that ablation of LGR5 from NB cancer cells led to drastic decrease in cancer cell growth in cell
cultures and tumor formation in animals. We also generated an ADC using an anti-LGR5 antibody and found
that the LGR5 ADC is highly effectively in killing NB cancer cells with high level of LGR5. The goals of this
project are to validate LGR5 as a potential target for the treatment of high-risk NBs using the ADC approach
and further improve the potency and efficacy of LGR5 ADC. We will generate a series of ADCs with different
payloads and determine their activities in blocking tumor growth in animal models. The project, if successful,
may lead to the validation of a new approach for the discovery and development of treatments of high-risk NBs
and drug candidates for further development.

## Key facts

- **NIH application ID:** 10356494
- **Project number:** 1R21CA267381-01
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Qingyun Liu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $182,325
- **Award type:** 1
- **Project period:** 2021-12-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10356494

## Citation

> US National Institutes of Health, RePORTER application 10356494, LGR5 antibody drug conjugate for the treatment of neuroblastoma (1R21CA267381-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10356494. Licensed CC0.

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