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© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Simple Summary

Pancreatic ductal adenocarcinoma (PDAC) is the twelfth most frequent cancer worldwide and the fourth leading cause of cancer-related deaths in the USA, and is projected to be ranked second by 2030. FOLFIRINOX or gemcitabine-abraxane, the current standard treatments for advanced PDAC, prolong survival by only several months in chemo-sensitive patients. Thus, there remains an urgent medical need to develop novel approaches to treat PDAC. Since the PDAC tumor microenvironment (TME) is highly immunosuppressive with M2 polarized macrophages (MΦ), inhibition of immunosuppressive M2 polarization offers a potentially robust approach to reactivate the immune system against PDAC. In this study, we developed a Saposin C (SapC)-coupled dioleoylphosphatidylglycerol (SapC-DOPG) that binds secreted heat shock protein 70 (Hsp70), which was recently shown to be secreted by PDAC cells and to be a potent mediator of TME immunosuppression. Our preclinical studies using mouse models of pancreatic cancer show that SapC-DOPG blocks Hsp70 actions and inhibits tumor growth. These preclinical studies suggest a promising immunotherapeutic approach to treat PDAC.

Details

Title
Targeting Hsp70 Immunosuppressive Signaling Axis with Lipid Nanovesicles: A Novel Approach to Treat Pancreatic Cancer
Author
Kaynak, Ahmet 1   VIAFID ORCID Logo  ; Vallabhapurapu, Subrahmanya D 1 ; Smith, Eric P 1 ; Davis, Harold W 1 ; Lewis, Clayton S 1 ; Ahn, Joseph 1 ; Muller, Petr 2   VIAFID ORCID Logo  ; Borek Vojtesek 2   VIAFID ORCID Logo  ; Stringer, Keith F 3 ; Franco, Robert S 1 ; Bogdanov, Vladimir Y 4   VIAFID ORCID Logo  ; Wen-Hai Shao 5   VIAFID ORCID Logo  ; Qi, Xiaoyang 1   VIAFID ORCID Logo 

 Division of Hematology & Oncology, Department of Internal Medicine, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA; [email protected] (A.K.); [email protected] (S.D.V.); [email protected] (E.P.S.); [email protected] (H.W.D.); [email protected] (C.S.L.); [email protected] (J.A.); [email protected] (R.S.F.) 
 Masaryk Memorial Cancer Institute, Research Centre for Applied Molecular Oncology, Zluty Kopec 7, 656 53 Brno, Czech Republic; [email protected] (P.M.); [email protected] (B.V.) 
 Division of Pathology and Laboratory Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA; [email protected] (K.F.S.) 
 Center for Scientific Review, National Institutes of Health, Bethesda, MD 20892, USA; (formerly at University of Cincinnati) [email protected] (V.Y.B.) 
 Division of Rheumatology, Allergy & Immunology, Department of Internal Medicine, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA; [email protected] (W.-H.S.) 
First page
1224
Publication year
2025
Publication date
2025
Publisher
MDPI AG
e-ISSN
20726694
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3188777646
Copyright
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.