001     294904
005     20250103102307.0
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|a 10.1080/2162402X.2024.2437917
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|a pmid:39651893
024 7 _ |2 ISSN
|a 2162-4011
024 7 _ |2 ISSN
|a 2162-402X
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037 _ _ |a DKFZ-2024-02614
041 _ _ |a English
082 _ _ |a 610
100 1 _ |0 P:(DE-HGF)0
|a Sofia, Liborio-Ramos
|b 0
|e First author
245 _ _ |a An integral membrane constitutively active heparanase enhances the tumor infiltration capability of NK cells.
260 _ _ |a Abingdon
|b Taylor & Franics
|c 2024
336 7 _ |2 DRIVER
|a article
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|2 PUB:(DE-HGF)
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|s 1733842239_4288
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|a ARTICLE
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|a JOURNAL_ARTICLE
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|2 EndNote
|a Journal Article
500 _ _ |a #EA:D122#LA:D122#
520 _ _ |a Eradication of cancer cells by the immune system requires extravasation, infiltration and progression of immune cells through the tumor extracellular matrix (ECM). These are also critical determinants for successful adoptive cell immunotherapy of solid tumors. Together with structural proteins, such as collagens and fibronectin, heparan sulfate (HS) proteoglycans are major components of the ECM. Heparanase 1 (HPSE) is the only enzyme known to have endoglycosidase activity that degrades HS. HPSE is expressed at high levels in almost all hematopoietic cells, which suggests that it plays a relevant role in immune cell migration through solid tissues. Besides, tumor cells express also HPSE as a way to facilitate tumor cell resettlement and metastasis. Therefore, an increase in HPSE in the tumor ECM would be detrimental. Here, we analyzed the effects of constitutive expression of an active, membrane-bound HPSE on the ability of human natural killer (NK) cells to infiltrate tumors and eliminate tumor cells. We demonstrate that NK cells expressing a chimeric active form of HPSE on the cell surface as an integral membrane protein, display significantly enhanced infiltration capability into spheroids of various cancer cell lines, as well as into xenograft tumors in immunodeficient mice. As a result, tumor growth was significantly suppressed without causing noticeable side effects. Altogether, our results suggest that a constitutively expressed active HSPE on the surface of immune effector cells enhances their capability to access and eliminate tumor cells. This strategy opens new possibilities for improving adoptive immune treatments using NK cells.
536 _ _ |0 G:(DE-HGF)POF4-314
|a 314 - Immunologie und Krebs (POF4-314)
|c POF4-314
|f POF IV
|x 0
588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de
650 _ 7 |2 Other
|a Adoptive cell transfer
650 _ 7 |2 Other
|a CAR
650 _ 7 |2 Other
|a T cell receptor
650 _ 7 |2 Other
|a cell therapy
650 _ 7 |2 Other
|a chimeric antigen receptor
650 _ 7 |2 Other
|a heparanase
650 _ 7 |2 Other
|a immunotherapy
650 _ 7 |2 Other
|a natural killer (NK) cells
650 _ 7 |0 EC 3.2.1.-
|2 NLM Chemicals
|a heparanase
650 _ 7 |0 EC 3.2.1.31
|2 NLM Chemicals
|a Glucuronidase
650 _ 2 |2 MeSH
|a Animals
650 _ 2 |2 MeSH
|a Humans
650 _ 2 |2 MeSH
|a Glucuronidase: metabolism
650 _ 2 |2 MeSH
|a Glucuronidase: genetics
650 _ 2 |2 MeSH
|a Killer Cells, Natural: immunology
650 _ 2 |2 MeSH
|a Mice
650 _ 2 |2 MeSH
|a Cell Line, Tumor
650 _ 2 |2 MeSH
|a Mice, SCID
650 _ 2 |2 MeSH
|a Cell Movement
650 _ 2 |2 MeSH
|a Neoplasms: immunology
650 _ 2 |2 MeSH
|a Neoplasms: pathology
650 _ 2 |2 MeSH
|a Neoplasms: therapy
650 _ 2 |2 MeSH
|a Mice, Inbred NOD
650 _ 2 |2 MeSH
|a Xenograft Model Antitumor Assays
700 1 _ |0 P:(DE-HGF)0
|a Isaac, Quiros-Fernandez
|b 1
|e First author
700 1 _ |a Neta, Ilan
|b 2
700 1 _ |a Soaad, Soboh
|b 3
700 1 _ |a Malik, Farhoud
|b 4
700 1 _ |0 P:(DE-HGF)0
|a Ruken, Süleymanoglu
|b 5
700 1 _ |0 P:(DE-HGF)0
|a Michele, Bennek
|b 6
700 1 _ |0 P:(DE-HGF)0
|a Sara, Calleja-Vara
|b 7
700 1 _ |a Martin, Müller
|b 8
700 1 _ |a Israel, Vlodavsky
|b 9
700 1 _ |0 P:(DE-He78)a30064f6b2d9ab959d35315d7668c091
|a Cid-Arregui, Angel
|b 10
|e Last author
|u dkfz
773 _ _ |0 PERI:(DE-600)2645309-5
|a 10.1080/2162402X.2024.2437917
|g Vol. 14, no. 1, p. 2437917
|n 1
|p 2437917
|t OncoImmunology
|v 14
|x 2162-4011
|y 2025
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LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21