Related Experiment Video
Updated: Feb 7, 2026
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Isolation of Proximal Fluids to Investigate the Tumor Microenvironment of Pancreatic Adenocarcinoma
Published on: November 5, 2020
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ProAgio, a Novel Integrin αvβ3 Targeted Cytotoxin, Suppresses Tumor Growth and Reprograms the PDAC Microenvironment
Dhana Sekhar Reddy Bandi1, Sujith Sarvesh1, Ganji Purnachandra Nagaraju1
1Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.
Biorxiv : the Preprint Server for Biology
|February 6, 2026
Summary
ProAgio combined with GPH therapy significantly improves pancreatic cancer tumor microenvironment by reducing hypoxia and enhancing anti-tumor immunity. This novel combination shows promise for future pancreatic ductal adenocarcinoma (PDAC) treatment strategies.
Area of Science:
- Oncology
- Immunology
- Medical Imaging
Background:
- Pancreatic ductal adenocarcinoma (PDAC) features a dense, hypoxic, and immune-suppressive tumor microenvironment (TME).
- Integrin αvβ3-expressing cells, including endothelial cells and cancer-associated fibroblasts (CAFs), are key contributors to the PDAC TME.
- ProAgio is a novel cytotoxin targeting integrin αvβ3, and GPH (gemcitabine, paricalcitol, hydroxychloroquine) influences the PDAC TME.
Purpose of the Study:
- To investigate the synergistic effects of ProAgio and GPH combination therapy on PDAC.
- To evaluate the impact of this combination on the tumor microenvironment, including hypoxia, immune cell infiltration, and stromal normalization.
- To assess tumor perfusion using dynamic contrast-enhanced MRI (DCE-MRI) in preclinical models and patients.
Main Methods:
- Utilized patient-derived xenograft (PDX) and orthotopic models of PDAC.
- Employed immunohistochemistry to assess hypoxia, epithelial-mesenchymal transition (EMT), and angiogenesis.
- Conducted multi-parameter flow cytometry for immune cell profiling and DCE-MRI for tumor perfusion analysis.
Main Results:
- ProAgio potentiated GPH's growth inhibitory effects by depleting integrin β3-expressing cells, leading to ECM remodeling, reduced vascular leakage, improved hypoxia, and reversed EMT.
- DCE-MRI demonstrated a significant increase in tumor perfusion post-ProAgio treatment in both mice and patients.
- Combination therapy markedly increased infiltration of γδ T cells, NKT cells, CD4+ effector T cells, and M1-like macrophages, while reducing myCAFs.
Conclusions:
- ProAgio, by targeting integrin αvβ3, effectively modulates the PDAC TME, enhancing perfusion, reducing hypoxia, reversing EMT, and mitigating immune suppression.
- The combination of ProAgio and GPH demonstrates potentiation of therapeutic effects and immunomodulatory benefits.
- Further clinical trials are warranted to evaluate ProAgio's role in potentiating GPH therapy for PDAC.
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