# Project 1: Employing CD11b-Agonists to Render PDAC Responsive to Immunotherapy

> **NIH NIH P50** · WASHINGTON UNIVERSITY · 2024 · $362,331

## Abstract

PROJECT SUMMARY
The potential of checkpoint immunotherapy to combat cancer has been established in several cancer types.
However, in pancreatic ductal adenocarcinoma (PDAC), checkpoint immunotherapy has not yet led to clinical
benefits. Although multiple factors likely contribute to checkpoint resistance, one significant factor is extensive
infiltration of PDACs by multiple lineages of immunosuppressive myeloid cells. These myeloid cells, which
include tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), drive T cell
exclusion and dysfunction. Thus, one promising therapeutic strategy is to reprogram these myeloid cells to
improve T cell-mediated immunity. Our team has recently developed an allosteric AGONIST of CD11b, GB1275.
Our published data demonstrate that CD11b-agonism rapidly repolarizes TAMs to support anti-tumor immunity
and combining CD11b-agonists with checkpoint immunotherapy leads to tumor regression and long-term survival
in pre-clinical PDAC models. These strong data drive our hypothesis that CD11b agonism reprograms the
PDAC tumor microenvironment to overcome resistance to checkpoint immunotherapy. To test this
hypothesis, we will:
Aim 1: Determine the safety and efficacy of GB1275, Gemcitabine and Abraxane and PD-1 blockade in
metastatic PDAC patients.
Aim 2: Determine the biomarkers of exposure, response, and resistance to GB1275 therapy in PDAC
patients.
Aim 3: Determine how tumor-intrinsic and extrinsic factors regulate the impact of CD11b agonist therapy.
Impact: These studies will investigate a novel approach to render PDAC responsive to immunotherapy.

## Key facts

- **NIH application ID:** 10916342
- **Project number:** 5P50CA272213-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** David G DeNardo
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $362,331
- **Award type:** 5
- **Project period:** 2023-08-28 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10916342

## Citation

> US National Institutes of Health, RePORTER application 10916342, Project 1: Employing CD11b-Agonists to Render PDAC Responsive to Immunotherapy (5P50CA272213-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10916342. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*