# A novel dual-carrier ultrasmall nanomedicine for the treatment of stroma-rich pancreatic cancer

> **NIH NIH R41** · DUO ONCOLOGY INC · 2024 · $55,000

## Abstract

EXECUTIVE SUMMARY
 Cancers rich in dense stromal tissue are more difficult to treat and carry a worse prognosis than cancers
without the stroma-rich phenotype. The fibrous stroma surrounding certain tumors effectively excludes many
current therapies, including antibody- or cell-based therapies and large (>30nm) nanoparticles. Duo Oncology
develops ultrasmall nanomedicines (10nm-30nm) that penetrate and accumulate in stroma-rich tumors but not
healthy organs. Specifically, our innovative ultrasmall nanomedicine, DUO-307, penetrates stroma rich tumors
and changes the tumor immune microenvironment through the combined actions of its gemcitabine prodrug
(PGEM) and co-encapsulated small molecule immunotherapy, chemokine receptor type 2 antagonist (CCR2a;
PF-04136309). It is a unique chemo-immunotherapy that is directly cytotoxic to the tumor and increases the
expression of programmed death receptor 1 (PD-1), which synergizes with immune checkpoint inhibitor
therapy.
 The proposal funded by the NCI and entitled, “A novel dual-carrier ultrasmall nanomedicine for the treatment
of stroma-rich pancreatic cancer”, aims to propel DUO-307 toward commercialization through the completion of
three specific aims:
• Aim 1, conducted in collaboration with Drs. Lance Munn and Gabriel Duda of Massachusetts General
 Hospital, will provide an optimized formulation of DUO-307. Our collaborators will grow and harvest human
 pancreatic cancer patient derived xenografts (PDX) to be used in a vascularized tissue explant (VTE)
 culture system. Tumor tissue samples will be exposed to increasing concentrations of PGEM to determine
 the quantity of chemokine ligand 2 (CCL2) produced when maximal GEM-associated apoptosis is
 achieved. We will then use a human monocyte chemotaxis assay to determine the optimal amount of
 CCR2a to co-load into our DUO-307 nanomedicine. The optimized formulation will then be characterized
 for particle size, drug loading efficiency, and stability. Progress has already been made toward the
 completion of this aim. Qualified PGEM nanoparticles were manufactured and delivered to Dr. Munn’s
 laboratory. PDX pancreatic tumor samples have been implanted into mice and once they reach the
 appropriate size will be harvested for experimental use in the VTE cultures.
• Aim 2 will evaluate the safety of the optimized DUO-307 formulation. A dose escalation study in naïve mice
 will be conducted to determine the maximum tolerated dose. A single cycle dosing schedule will be used
 and terminal clinical chemistry and blood cell counts will be the primary outcomes of interest.
• Aim 3 will test the efficacy of DUO-307 in combination with anti-PD-1 therapy in an orthotopic KrasG12D/+;
 LSL-Trp53R172H/+; Pdx1-Cre (KPC) mouse model of pancreatic cancer. This aim will be conducted in
 collaboration with Dr. Song Li at the University of Pittsburgh and will evaluate DUO-307’s ability to inhibit
 tumor growth, reduce tumor associated macrophage populations, and ultimatel...

## Key facts

- **NIH application ID:** 10987908
- **Project number:** 3R41CA285174-01S1
- **Recipient organization:** DUO ONCOLOGY INC
- **Principal Investigator:** Katherine Marie Eichinger
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $55,000
- **Award type:** 3
- **Project period:** 2024-03-04 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10987908

## Citation

> US National Institutes of Health, RePORTER application 10987908, A novel dual-carrier ultrasmall nanomedicine for the treatment of stroma-rich pancreatic cancer (3R41CA285174-01S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10987908. Licensed CC0.

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