# R21: A novel antibody-drug conjugate for treatment of squamous cell lung carcinoma

> **NIH NIH R21** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2022 · $192,844

## Abstract

A novel antibody-drug conjugate for treatment of squamous cell lung carcinoma
 Project Summary
With few available treatments, lung squamous cell carcinoma (SCC) has a 5-year survival of only 21%. This
proposal outlines a novel antibody-drug conjugate (ADC) therapy for lung SCC, which targets and delivers a
highly potent chemotherapy monomethyl auristatin E (MMAE) to G protein-coupled receptor 87 (GPR87)-
overexpressing SCC tumors. ADCs combine the advantages of the high specificity of a targeting antibody and
the high potency of a cytotoxic drug, and therefore, have the potential to improve the efficacy of the drug and
reduce off-target toxicity. We will employ a new reliable approach for drug conjugation that utilizes
supramolecular assembly of coiled coil peptides. This method allows site-specific, uniform loading of two drug
molecules at the Fc region per antibody and maintains targeting specificity of the Fab region. The strong binding
affinity of the coiled coils enhances ADC stability and prevents premature release of the drug. Moreover, the
approach allows facile pairing of antibodies and drugs under mild aqueous conditions. The proposed
experiments will test the hypothesis that an αGPR87 antibody-MMAE conjugate will target lung tumors,
reduce systemic toxicity of MMAE, and extend survival, compared to a conventional ADC and MMAE
alone in a SCC patient-derived xenograft (PDX) model. Importantly, well-characterized materials and
rigorous experimental designs are established in this proposal with essential cross-disciplinary collaborations
and expertise. The aims of this exploratory and developmental proposal are as follow. Aim 1 determines
immunogenicity of the ADC components, and plasma stability, tumor binding and cytotoxicity of the
ADC in human lung cancer and normal cell lines. Aim 2 evaluates biodistribution, PK, systemic toxicity
and efficacy of the ADC in a SCC PDX model. Successful development of this ADC delivery platform will
generate a novel targeted therapy with minimal off-target toxicity for SCC. Our supramolecular self-assembly
conjugation approach also provides a versatile conjugation strategy applicable to other antibody-drug pairs for
treatment of other cancers and diseases.

## Key facts

- **NIH application ID:** 10510002
- **Project number:** 1R21CA273645-01
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** MARK W. GRINSTAFF
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $192,844
- **Award type:** 1
- **Project period:** 2022-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10510002

## Citation

> US National Institutes of Health, RePORTER application 10510002, R21: A novel antibody-drug conjugate for treatment of squamous cell lung carcinoma (1R21CA273645-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10510002. Licensed CC0.

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