000289779 001__ 289779 000289779 005__ 20250525020712.0 000289779 0247_ $$2doi$$a10.1002/jmv.29630 000289779 0247_ $$2pmid$$apmid:38659368 000289779 0247_ $$2ISSN$$a0146-6615 000289779 0247_ $$2ISSN$$a1096-9071 000289779 0247_ $$2altmetric$$aaltmetric:163098936 000289779 037__ $$aDKFZ-2024-00858 000289779 041__ $$aEnglish 000289779 082__ $$a610 000289779 1001_ $$0P:(DE-HGF)0$$aQuiros-Fernandez, Isaac$$b0$$eFirst author 000289779 245__ $$aDual T cell receptor/chimeric antigen receptor engineered NK-92 cells targeting the HPV16 E6 oncoprotein and the tumor-associated antigen L1CAM exhibit enhanced cytotoxicity and specificity against tumor cells. 000289779 260__ $$aBognor Regis [u.a.]$$bWiley$$c2024 000289779 3367_ $$2DRIVER$$aarticle 000289779 3367_ $$2DataCite$$aOutput Types/Journal article 000289779 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1714048879_1932 000289779 3367_ $$2BibTeX$$aARTICLE 000289779 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000289779 3367_ $$00$$2EndNote$$aJournal Article 000289779 500__ $$a#EA:D122#LA:D122# 000289779 520__ $$aThe human papillomavirus type 16 (HPV16) causes a large fraction of genital and oropharyngeal carcinomas. To maintain the transformed state, the tumor cells must continuously synthesize the E6 and E7 viral oncoproteins, which makes them tumor-specific antigens. Indeed, specific T cell responses against them have been well documented and CD8+ T cells engineered to express T cell receptors (TCRs) that recognize epitopes of E6 or E7 have been tested in clinical studies with promising results, yet with limited clinical success. Using CD8+ T cells from peripheral blood of healthy donors, we have identified two novel TCRs reactive to an unexplored E618-26 epitope. These TCRs showed limited standalone cytotoxicity against E618-26-HLA-A*02:01-presenting tumor cells. However, a single-signaling domain chimeric antigen receptor (ssdCAR) targeting L1CAM, a cell adhesion protein frequently overexpressed in HPV16-induced cancer, prompted a synergistic effect that significantly enhanced the cytotoxic capacity of NK-92/CD3/CD8 cells armored with both TCR and ssdCAR when both receptors simultaneously engaged their respective targets, as shown by live microscopy of 2-D and 3-D co-cultures. Thus, virus-specific TCRs from the CD8+ T cell repertoire of healthy donors can be combined with a suitable ssdCAR to enhance the cytotoxic capacity of the effector cells and, indirectly, their specificity. 000289779 536__ $$0G:(DE-HGF)POF4-314$$a314 - Immunologie und Krebs (POF4-314)$$cPOF4-314$$fPOF IV$$x0 000289779 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de 000289779 650_7 $$2Other$$aCAR 000289779 650_7 $$2Other$$aT cell receptor 000289779 650_7 $$2Other$$aadoptive cell transfer 000289779 650_7 $$2Other$$acell therapy 000289779 650_7 $$2Other$$acervical cancer 000289779 650_7 $$2Other$$achimeric antigen receptor 000289779 650_7 $$2Other$$ahuman papillomavirus 000289779 650_7 $$2Other$$aimmunotherapy 000289779 650_7 $$2NLM Chemicals$$aOncogene Proteins, Viral 000289779 650_7 $$2NLM Chemicals$$aE6 protein, Human papillomavirus type 16 000289779 650_7 $$2NLM Chemicals$$aReceptors, Chimeric Antigen 000289779 650_7 $$2NLM Chemicals$$aReceptors, Antigen, T-Cell 000289779 650_7 $$2NLM Chemicals$$aRepressor Proteins 000289779 650_2 $$2MeSH$$aHumans 000289779 650_2 $$2MeSH$$aOncogene Proteins, Viral: immunology 000289779 650_2 $$2MeSH$$aOncogene Proteins, Viral: genetics 000289779 650_2 $$2MeSH$$aReceptors, Chimeric Antigen: immunology 000289779 650_2 $$2MeSH$$aReceptors, Chimeric Antigen: genetics 000289779 650_2 $$2MeSH$$aReceptors, Antigen, T-Cell: immunology 000289779 650_2 $$2MeSH$$aReceptors, Antigen, T-Cell: genetics 000289779 650_2 $$2MeSH$$aRepressor Proteins: immunology 000289779 650_2 $$2MeSH$$aRepressor Proteins: genetics 000289779 650_2 $$2MeSH$$aCD8-Positive T-Lymphocytes: immunology 000289779 650_2 $$2MeSH$$aKiller Cells, Natural: immunology 000289779 650_2 $$2MeSH$$aHuman papillomavirus 16: immunology 000289779 650_2 $$2MeSH$$aHuman papillomavirus 16: genetics 000289779 650_2 $$2MeSH$$aCytotoxicity, Immunologic 000289779 650_2 $$2MeSH$$aCell Line, Tumor 000289779 7001_ $$0P:(DE-HGF)0$$aLibório-Ramos, Sofia$$b1 000289779 7001_ $$0P:(DE-He78)22cadd1a84ded1078feece66c8664d59$$aLeifert, Lena$$b2 000289779 7001_ $$0P:(DE-He78)af9892a34bf8a8a9cf0e7a11a8617645$$aSchönfelder, Bruno$$b3$$udkfz 000289779 7001_ $$aVlodavsky, Israel$$b4 000289779 7001_ $$0P:(DE-He78)a30064f6b2d9ab959d35315d7668c091$$aCid-Arregui, Angel$$b5$$eLast author$$udkfz 000289779 773__ $$0PERI:(DE-600)1475090-9$$a10.1002/jmv.29630$$gVol. 96, no. 5, p. e29630$$n5$$pe29630$$tJournal of medical virology$$v96$$x0146-6615$$y2024 000289779 8564_ $$uhttps://inrepo02.dkfz.de/record/289779/files/Journal%20of%20Medical%20Virology%20-%202024%20-%20Quiros%E2%80%90Fernandez%20-%20Dual%20T%20cell%20receptor%20chimeric%20antigen%20receptor%20engineered%20NK%E2%80%9092.pdf 000289779 8564_ $$uhttps://inrepo02.dkfz.de/record/289779/files/Journal%20of%20Medical%20Virology%20-%202024%20-%20Quiros%E2%80%90Fernandez%20-%20Dual%20T%20cell%20receptor%20chimeric%20antigen%20receptor%20engineered%20NK%E2%80%9092.pdf?subformat=pdfa$$xpdfa 000289779 909CO $$ooai:inrepo02.dkfz.de:289779$$pVDB 000289779 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b0$$kDKFZ 000289779 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b1$$kDKFZ 000289779 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)22cadd1a84ded1078feece66c8664d59$$aDeutsches Krebsforschungszentrum$$b2$$kDKFZ 000289779 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)af9892a34bf8a8a9cf0e7a11a8617645$$aDeutsches Krebsforschungszentrum$$b3$$kDKFZ 000289779 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)a30064f6b2d9ab959d35315d7668c091$$aDeutsches Krebsforschungszentrum$$b5$$kDKFZ 000289779 9131_ $$0G:(DE-HGF)POF4-314$$1G:(DE-HGF)POF4-310$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vImmunologie und Krebs$$x0 000289779 9141_ $$y2024 000289779 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz$$d2023-10-21$$wger 000289779 915__ $$0StatID:(DE-HGF)3001$$2StatID$$aDEAL Wiley$$d2023-10-21$$wger 000289779 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bJ MED VIROL : 2022$$d2023-10-21 000289779 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2023-10-21 000289779 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2023-10-21 000289779 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2023-10-21 000289779 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2023-10-21 000289779 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2023-10-21 000289779 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2023-10-21 000289779 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - 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