Home > Institute Collections > W500 > Development of DPP-4-resistant CXCL9-Fc and CXCL10-Fc chemokines for effective cancer immunotherapy. > print

001     306696
005     20251203120311.0
024 7 _ |a 10.1073/pnas.2501791122
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024 7 _ |a pmid:40238455
|2 pmid
024 7 _ |a pmc:PMC12037015
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024 7 _ |a 0027-8424
|2 ISSN
024 7 _ |a 1091-6490
|2 ISSN
037 _ _ |a DKFZ-2025-02686
041 _ _ |a English
082 _ _ |a 500
100 1 _ |a Lugassy, Jennie
|b 0
245 _ _ |a Development of DPP-4-resistant CXCL9-Fc and CXCL10-Fc chemokines for effective cancer immunotherapy.
260 _ _ |a Washington, DC
|c 2025
|b National Acad. of Sciences
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|b journal
|m journal
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|s 1764759727_1331671
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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500 _ _ |a #DKFZ-MOST-Ca188#
520 _ _ |a CXCR3 is a chemokine receptor for three ligands: CXCL9, CXCL10, and CXCL11. Accumulating evidence, including data presented here, suggests that the interaction between CXCL9/CXCL10 and CXCR3 not only attracts CXCR3+ T cells but also promotes the induction of IFNγ-high effector/cytotoxic CD4+ and CD8+ T cells, establishing a CXCL9/10-CXCR3-IFNγ self-amplifying cycle that promotes efficient cancer cell killing. One of the homeostatic mechanisms that may limit this cycle is the cleavage of the two N-terminal amino acids of these chemokines by Dipeptidyl Peptidase IV (DPP-4). The modified chemokines retain their ability to bind CXCR3 but no longer activate it, becoming competitive antagonists to native CXCL9/CXCL10. To develop a DPP-4-resistant variant, we combined biochemical analysis with computational modeling, demonstrating that the addition of N-terminal glutamine (Q) to CXCL9-Fc and CXCL10-Fc rendered them fully active CXCR3 agonists, yet resistant to DPP-4 cleavage. Preclinical evaluations imply that they offer significant therapeutic potential in cancer immunotherapy.
588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de
650 _ 7 |a CXCL10
|2 Other
650 _ 7 |a CXCR3
|2 Other
650 _ 7 |a DPP-4
|2 Other
650 _ 7 |a T cell subsets
|2 Other
650 _ 7 |a immunotherapy
|2 Other
650 _ 7 |a Chemokine CXCL9
|2 NLM Chemicals
650 _ 7 |a Chemokine CXCL10
|2 NLM Chemicals
650 _ 7 |a Dipeptidyl Peptidase 4
|0 EC 3.4.14.5
|2 NLM Chemicals
650 _ 7 |a Receptors, CXCR3
|2 NLM Chemicals
650 _ 7 |a CXCR3 protein, human
|2 NLM Chemicals
650 _ 7 |a CXCL9 protein, human
|2 NLM Chemicals
650 _ 7 |a CXCL10 protein, human
|2 NLM Chemicals
650 _ 7 |a Immunoglobulin Fc Fragments
|2 NLM Chemicals
650 _ 7 |a DPP4 protein, human
|0 EC 3.4.14.5
|2 NLM Chemicals
650 _ 2 |a Chemokine CXCL9: genetics
|2 MeSH
650 _ 2 |a Chemokine CXCL9: metabolism
|2 MeSH
650 _ 2 |a Chemokine CXCL9: immunology
|2 MeSH
650 _ 2 |a Chemokine CXCL9: chemistry
|2 MeSH
650 _ 2 |a Chemokine CXCL10: genetics
|2 MeSH
650 _ 2 |a Chemokine CXCL10: metabolism
|2 MeSH
650 _ 2 |a Chemokine CXCL10: immunology
|2 MeSH
650 _ 2 |a Chemokine CXCL10: chemistry
|2 MeSH
650 _ 2 |a Dipeptidyl Peptidase 4: metabolism
|2 MeSH
650 _ 2 |a Dipeptidyl Peptidase 4: genetics
|2 MeSH
650 _ 2 |a Receptors, CXCR3: metabolism
|2 MeSH
650 _ 2 |a Receptors, CXCR3: immunology
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Immunotherapy: methods
|2 MeSH
650 _ 2 |a Neoplasms: therapy
|2 MeSH
650 _ 2 |a Neoplasms: immunology
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Immunoglobulin Fc Fragments: genetics
|2 MeSH
650 _ 2 |a Immunoglobulin Fc Fragments: immunology
|2 MeSH
650 _ 2 |a Cell Line, Tumor
|2 MeSH
650 _ 2 |a CD8-Positive T-Lymphocytes: immunology
|2 MeSH
700 1 _ |a Abdala-Saleh, Noor
|b 1
700 1 _ |a Jarrous, Ghada
|b 2
700 1 _ |a Turky, Abeer
|b 3
700 1 _ |a Saidemberg, Daniel
|0 0009-0008-6684-7876
|b 4
700 1 _ |a Ridner-Bahar, Gabriela
|0 0009-0009-8666-1320
|b 5
700 1 _ |a Berger, Nir
|0 0000-0002-7008-9667
|b 6
700 1 _ |a Bar-On, Dana
|b 7
700 1 _ |a Taura, Tetsuya
|b 8
700 1 _ |a Wilson, David
|b 9
700 1 _ |a Karin, Nathan
|0 0000-0003-2355-6661
|b 10
773 _ _ |a 10.1073/pnas.2501791122
|g Vol. 122, no. 16, p. e2501791122
|0 PERI:(DE-600)1461794-8
|n 16
|p e2501791122
|t Proceedings of the National Academy of Sciences of the United States of America
|v 122
|y 2025
|x 0027-8424
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