# A treatment drug for triple negative breast cancer

> **NIH NIH U44** · PRODA BIOTECH, LLC · 2023 · $999,562

## Abstract

Summary
Triple negative breast cancers (TNBC) are devastating diseases with a median survival of less
than 1-year for patients with metastatic disease. TNBC patients with tumor of high fibrotic stroma
have even worse prognosis. There are no specific targeted therapies available for TNBC, and the
only treatment option is broadly cytotoxic chemotherapy drugs, despite less effective and strong
unwanted side effects of such drugs. One major barrier to efficacy of anti-tumor therapeutics is
the dense fibrotic stromal and dysregulated tumor blood vessels which contribute to failure of
therapies. Evidence suggests that cancer associated fibroblasts (CAF) produce the stromal
collagen. The ECM laid down by CAF is considered to be one of the major contributors of
resistance to established therapies of the diseases. TNBC has high angiogenic activity. Dense
tumor vasculature associated with a shorter time from diagnosis to relapse and from relapse to
death. The dysregulated vessel structure in TNBC tumor often leads to resistance to blood flow
into tumor, which is another important barrier for drug delivery. Depleting CAF and abrogating
tumor angiogenesis could significantly improve efficacy of existing TNBC cancer treatments.
However, currently, there are no approved therapies that are able to deplete CAF and tumor
angiogenesis in TNBC cancer. We have developed a novel therapeutic protein (ProAgio) using
rational protein design. ProAgio is designed to target integrin v3 at a novel site (not the ligand
binding site). ProAgio specifically induces apoptosis of integrin v3 expressing cells with high
efficacy by a novel mechanism of drug action (recruiting & activating caspase 8 at cytoplasmic
domain of). We reasoned that, since both CAF and angiogenic endothelial cells (aEC) express
high levels of integrin v3, and since ProAgio is very effective in inducing apoptosis of integrin
v3 expressing cells, ProAgio should both deplete CAF, eliminate intratumoral angiogenic blood
vessels in and around TNBC tumors. This unique strategy may prove advantageous in treatment
of TNBC. The main objective of this direct phase II SBIR application is to generate a definitive
dataset to enable the development of ProAgio as a viable therapeutic option for TNBC patients.
Characterization of the toxicity and tolerability and determine the maximum tolerated dose (MTD)
and recommended phase II dose (RP2D) of ProAgio as a single agent is on-going. Aim 1 will
characterize the toxicity and tolerability and determine the recommended phase II dose (RP2D)
of ProAgio in combination with gemcitabine (Gem). Aim 2 will obtain preliminary anti-cancer
activity data of ProAgio and ProAgio + Gem in TNBC patients. Aim 3 will analyze the effects of
ProAgio in patient tumor to validate the mechanism of drug action in patients. This clinical study
project will explore new therapeutic avenue for TNBC patients. Our goal is that, through our study,
we will introduce a new treatment approach for ...

## Key facts

- **NIH application ID:** 10643890
- **Project number:** 5U44CA268345-02
- **Recipient organization:** PRODA BIOTECH, LLC
- **Principal Investigator:** Zhi-Ren Liu
- **Activity code:** U44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $999,562
- **Award type:** 5
- **Project period:** 2022-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10643890

## Citation

> US National Institutes of Health, RePORTER application 10643890, A treatment drug for triple negative breast cancer (5U44CA268345-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10643890. Licensed CC0.

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