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The Efficacy of Targeted Monoclonal IgA Antibodies Against Pancreatic Ductal Adenocarcinoma

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Titel: The Efficacy of Targeted Monoclonal IgA Antibodies Against Pancreatic Ductal Adenocarcinoma
Autoren: Léon Raymakers, Elsemieke M. Passchier, Meggy E. L. Verdonschot, Mitchell Evers, Chilam Chan, Karel C. Kuijpers, G. Mihaela Raicu, I. Quintus Molenaar, Hjalmar C. van Santvoort, Karin Strijbis, Martijn P. W. Intven, Lois A. Daamen, Jeanette H. W. Leusen, Patricia A. Olofsen
Quelle: Cells
Cells, Vol 14, Iss 9, p 632 (2025)
Verlagsinformationen: MDPI AG, 2025.
Publikationsjahr: 2025
Schlagwörter: Epithelial Cell Adhesion Molecule/metabolism, Neutrophils, Monoclonal/therapeutic use, CD47 Antigen, mAbs, Antibodies, Article, Cell Line, neutrophils, Antigens, Neoplasm, Cell Line, Tumor, Tumor Microenvironment, Humans, Antigens, PMNs, Tumor, QH573-671, CD47 Antigen/metabolism, Carcinoma, Neutrophils/immunology, Mucin-1, Antibodies, Monoclonal, Epithelial Cell Adhesion Molecule, Pancreatic Ductal/immunology, Tumor Microenvironment/drug effects, Immunoglobulin A, Pancreatic Neoplasms, polymorphonuclear cells, Neoplasm/metabolism, Immunoglobulin A/immunology, Mucin-1/metabolism, monoclonal antibodies, Immunotherapy, Pancreatic Neoplasms/immunology, Cytology, IgA, Carcinoma, Pancreatic Ductal
Beschreibung: The efficacy of immunotherapy in pancreatic ductal adenocarcinoma (PDAC) remains limited. The tumor microenvironment (TME), characterized by the accumulation of suppressive myeloid cells including neutrophils, attributes to immunotherapy resistance in PDAC. IgA monoclonal antibodies (mAbs) can activate neutrophils to kill tumor cells; this can be further enhanced by blocking the myeloid immune checkpoint CD47. In this study, we investigated the potential of this therapeutic strategy for PDAC. We determined the expression of tumor-associated antigens (TAAs) on PDAC cell lines and fresh patient samples, and the results showed that the TAAs epithelial cell adhesion molecule (EpCAM), trophoblast cell surface antigen 2 (TROP2) and mucin-1 (MUC1), as well as CD47 were consistently expressed on PDAC. In line with this, we showed that IgA mAbs against EpCAM can activate neutrophils to lyse various PDAC cell lines and tumor cells, which can be augmented by addition of CD47 blockade. In addition, we observed that neutrophils were present in patient tumors and expressed the receptor for IgA. In conclusion, our results indicate that a combination of IgA mAb with CD47 blockade is a promising preclinical treatment strategy for PDAC, which merits further investigation.
Publikationsart: Article
Other literature type
Sprache: English
ISSN: 2073-4409
DOI: 10.3390/cells14090632
Zugangs-URL: https://pubmed.ncbi.nlm.nih.gov/40358156
https://doaj.org/article/3bb8d71d2de94ef386452eec0b97fe8a
https://research-portal.uu.nl/en/publications/49b313e6-0873-4718-a461-dcedcd48408a
https://doi.org/10.3390/cells14090632
Rights: CC BY
Dokumentencode: edsair.doi.dedup.....7664f99fd7b04af5e36de3adb7c0d22b
Datenbank: OpenAIRE
Beschreibung
Abstract:The efficacy of immunotherapy in pancreatic ductal adenocarcinoma (PDAC) remains limited. The tumor microenvironment (TME), characterized by the accumulation of suppressive myeloid cells including neutrophils, attributes to immunotherapy resistance in PDAC. IgA monoclonal antibodies (mAbs) can activate neutrophils to kill tumor cells; this can be further enhanced by blocking the myeloid immune checkpoint CD47. In this study, we investigated the potential of this therapeutic strategy for PDAC. We determined the expression of tumor-associated antigens (TAAs) on PDAC cell lines and fresh patient samples, and the results showed that the TAAs epithelial cell adhesion molecule (EpCAM), trophoblast cell surface antigen 2 (TROP2) and mucin-1 (MUC1), as well as CD47 were consistently expressed on PDAC. In line with this, we showed that IgA mAbs against EpCAM can activate neutrophils to lyse various PDAC cell lines and tumor cells, which can be augmented by addition of CD47 blockade. In addition, we observed that neutrophils were present in patient tumors and expressed the receptor for IgA. In conclusion, our results indicate that a combination of IgA mAb with CD47 blockade is a promising preclinical treatment strategy for PDAC, which merits further investigation.
ISSN:20734409
DOI:10.3390/cells14090632