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000289779 041__ $$aEnglish
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000289779 1001_ $$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$$c2024
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000289779 520__ $$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$$x0
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000289779 650_7 $$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
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