# Phage Display for Improved Peptide-Based Tumor Targeting and Imaging Agents

> **NIH VA I01** · HARRY S. TRUMAN MEMORIAL VA HOSPITAL · 2021 · —

## Abstract

Aggressive forms of cancer are a leading health problem for United States Veterans. While most cancers
are treatable in their earliest forms, gender-related cancers including those of the breast and prostate are
often fatal when diagnosed at advanced and/or metastatic stages. In 2020, these cancers will account for over
75,400 annual deaths in the general population, with morbidity rates significantly higher in the Veteran
population. While most patients initially respond to treatment, they often relapse and develop aggressive and
drug resistant tumors. A promising approach to better detect and treat these types of cancers may be through
development of agents that target drug resistance biomarkers that associate with cancer stem cells (CSCs).
CSCs make up a small proportion of a tumor but drive tumor aggressiveness and drug resistance. There are
few validated CSC biomarkers, and most are not cancer-specific. Our laboratory is at the forefront of new
biomarker and CSC identification using bacteriophage (phage) display. Peptides and antibody (Ab) fragments
that bind the breast and prostate associated Thomsen-Friedenreich carbohydrate antigen, (TF), the lectin
galectin-3 (gal-3) that binds TF and inhibits immune response, and CD444v6 have been obtained. These
antigens are involved in cell adhesion, angiogenesis, immune regulation, and cell signaling, and are thought to
represent CSC biomarkers. Further, we demonstrated that CD44v6 binds gal-3 through TF interaction,
suggesting this triad may represent a novel target to probe CSCs, tumor growth and immune surveillance.
 Both Abs and peptides have been used with mixed success in cancer imaging and therapy. In terms of
Abs their large size can cause immunogenic problems and long distribution times that once radiolabeled often
leads to organ and tissue damage. Conversely, peptides, particularly those from phage display are
usually hydrophobic and often suffer from poor affinity and tumor uptake. Two different tacks will be
employed that overcome these drawbacks. A pretargeted “click” chemistry approach which decouples the
tumor-targeting step from the radioimaging or radiotherapy step can be employed. This pretargeted approach
is based on the rapid and highly specific cycloaddition reaction that occurs between the trans-cyclooctene
(TCO) on the tumor by allowing the unlabeled targeting Ab to circulate and bind the target. Subsequently,
injection of a small molecule radiolabeled probe with rapid pharmacokinetics and high affinity for the
pretargeted Ab, will result in higher tumor to normal tissue uptake ratios compared to direct labeled Abs. The
second tack will be to conjugate small peptides to a nanoparticle for multi-peptide display. Cornell prime dots
(C' dots) are a new and well-characterized nanoparticle platform that offer both multimodal-targeted imaging
and therapy, and multiplexing biomarker interrogation. C' dots are silica core-shell PEG nanoparticles that
exhibit favorable clearance from th...

## Key facts

- **NIH application ID:** 10115970
- **Project number:** 2I01BX000964-08A1
- **Recipient organization:** HARRY S. TRUMAN MEMORIAL VA HOSPITAL
- **Principal Investigator:** SUSAN L DEUTSCHER
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 2
- **Project period:** 2011-07-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10115970

## Citation

> US National Institutes of Health, RePORTER application 10115970, Phage Display for Improved Peptide-Based Tumor Targeting and Imaging Agents (2I01BX000964-08A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10115970. Licensed CC0.

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