# Project 3: Oncofetal Glycosaminoglycans as Molecular Targets in Prostate Cancer

> **NIH NIH P50** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2021 · $72,067

## Abstract

PROJECT SUMMARY/ABSTRACT
Anomalous expression of glycosaminoglycans (GAG) such as chondroitin sulfate (CS) has been recognized in
prostate cancer (PC) for decades. While CS is a potentially attractive tumor antigen in PC, utility of CS variants
as therapeutic targets represent a technical challenge due to inherent low avidity of antibodies towards complex
GAG structures. Embracing that challenge, we have developed a cross-disciplinary CS targeting strategy for PC
based on engineered recombinant proteins from the malaria parasite Plasmodium falciparum. As a survival
strategy to avoid host clearance, the malaria parasite has evolved a protein VAR2CSA that mediates high affinity
binding to distinct CS in the placenta. PC express the same type of CS as placental trophoblasts thus
recombinant malarial VAR2CSA (rVAR2) proteins can be re-purposed to target oncofetal CS (ofCS) modification
in PC. Expression of ofCS in primary PC is not restricted to the tumor epithelium but is also present in the stromal
cell compartment. Moreover, the rVAR2 protein can detect and isolate circulating tumor cells (CTCs) from
complex blood samples. Finally, we have an rVAR2-Drug Conjugate (VDC886) able to engage ofCS-expressing
PC cells in vitro and in vivo. Combined, our technology can access and target a tumor-selective GAG structure
in PC for diagnostic and therapeutic applications.
We hypothesize that our rVAR2-based ofCS-targeting system constitutes a novel therapeutic and diagnostic
opportunity in human PC. Our hypothesis will be tested in the following Specific Aims:
Aim 1: Preclinical evaluation of VDC886 as a novel treatment for metastatic CRPC (mCRPC).
Aim 2: Visualization of metastatic PC lesions by ofCS PET imaging.
Aim 3: Design and execute a phase I trial of VDC886 in mCRPC.

## Key facts

- **NIH application ID:** 10247717
- **Project number:** 5P50CA097186-19
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Mads Daugaard
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $72,067
- **Award type:** 5
- **Project period:** 2002-09-19 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247717

## Citation

> US National Institutes of Health, RePORTER application 10247717, Project 3: Oncofetal Glycosaminoglycans as Molecular Targets in Prostate Cancer (5P50CA097186-19). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10247717. Licensed CC0.

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