# Targeting CD133 for imaging and therapy in prostate cancer

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $355,706

## Abstract

ABSTRACT
 Aggressive variant prostate cancer (AVPC) arises in men who have failed treatment with second-generation
anti-androgen therapy. Not driven by the androgen receptor-signaling axis, effective treatment options do not
exist for AVPC and new, innovative therapies are urgently needed. Critical to the development of novel
therapeutics is the ability to accurately image disease burden in AVPC patients. An imaging modality that can
detect both the bone and visceral metastases associated with AVPC does not exist. The overall goal of this
project is to develop positron emission tomography (PET) imaging probes and radioimmunotherapy (RIT) agents
by targeting a newly identified cell-surface antigen unique to AVPC with novel antibody constructs. Using human
antibody phage display, we recently identified a single chain variable fragment (scFv) that specifically bound to
a glycosylation-independent epitope on the peptide backbone of the transmembrane protein CD133. Often
characterized as a cancer stem cell marker, the function of CD133 in cancer is unknown. All commercially
available antibodies for CD133 recognize glycosylation-dependent epitopes that vary between cells and at
different stages of the cell cycle. Immunohistochemistry (IHC) with these antibodies yield inconsistent results
and poor staining quality; thus contributing to our limited knowledge of CD133. Our scFv for CD133, termed A10,
was converted into a full-length immunoglobulin (IA10) for IHC analysis on patient biopsies and tissue
microarrays. Remarkably, we found that CD133 was only expressed in bone and visceral metastases of men
who had developed AVPC. As a single-photon emission computed tomography imaging agent, IA10 was able to
image CD133 expression in vivo. In biodistribution studies, IA10 and a smaller minibody construct version
(MA10) both demonstrated high tumor uptake and favorable pharmacokinetics. The high tumor uptake of the
A10 antibody constructs was the direct result of their rapid internalization by CD133-expressing cells making
them ideal candidates for longitudinal PET imaging and RIT. In this proposal, we will evaluate the utility of IA10
and MA10 as PET probes in cell line-derived and patient-derived xenograft models of AVPC and evaluate CD133
as a pharmacodynamic biomarker (Aim 1) then determine the therapeutic potential of IA10 radiolabeled with
177Lu for beta particle RIT in subcutaneous and metastatic xenografts using single and fractionated doses (Aim
2). Our preliminary data strongly suggest that we have developed potent tools for AVPC that possess the
potential to result in a dramatic shift in how the disease is treated.

## Key facts

- **NIH application ID:** 10470959
- **Project number:** 5R01CA237272-04
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Aaron Matthew LeBeau
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $355,706
- **Award type:** 5
- **Project period:** 2021-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10470959

## Citation

> US National Institutes of Health, RePORTER application 10470959, Targeting CD133 for imaging and therapy in prostate cancer (5R01CA237272-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10470959. Licensed CC0.

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