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| 024 | 7 | _ | |a 10.1002/jmv.29630 |2 doi |
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| 024 | 7 | _ | |a 0146-6615 |2 ISSN |
| 024 | 7 | _ | |a 1096-9071 |2 ISSN |
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| 037 | _ | _ | |a DKFZ-2024-00858 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Quiros-Fernandez, Isaac |0 P:(DE-HGF)0 |b 0 |e First author |
| 245 | _ | _ | |a Dual 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. |
| 260 | _ | _ | |a Bognor Regis [u.a.] |c 2024 |b Wiley |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1714048879_1932 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
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| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 500 | _ | _ | |a #EA:D122#LA:D122# |
| 520 | _ | _ | |a The 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. |
| 536 | _ | _ | |a 314 - Immunologie und Krebs (POF4-314) |0 G:(DE-HGF)POF4-314 |c POF4-314 |f POF IV |x 0 |
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| 650 | _ | 7 | |a CAR |2 Other |
| 650 | _ | 7 | |a T cell receptor |2 Other |
| 650 | _ | 7 | |a adoptive cell transfer |2 Other |
| 650 | _ | 7 | |a cell therapy |2 Other |
| 650 | _ | 7 | |a cervical cancer |2 Other |
| 650 | _ | 7 | |a chimeric antigen receptor |2 Other |
| 650 | _ | 7 | |a human papillomavirus |2 Other |
| 650 | _ | 7 | |a immunotherapy |2 Other |
| 650 | _ | 7 | |a Oncogene Proteins, Viral |2 NLM Chemicals |
| 650 | _ | 7 | |a E6 protein, Human papillomavirus type 16 |2 NLM Chemicals |
| 650 | _ | 7 | |a Receptors, Chimeric Antigen |2 NLM Chemicals |
| 650 | _ | 7 | |a Receptors, Antigen, T-Cell |2 NLM Chemicals |
| 650 | _ | 7 | |a Repressor Proteins |2 NLM Chemicals |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Oncogene Proteins, Viral: immunology |2 MeSH |
| 650 | _ | 2 | |a Oncogene Proteins, Viral: genetics |2 MeSH |
| 650 | _ | 2 | |a Receptors, Chimeric Antigen: immunology |2 MeSH |
| 650 | _ | 2 | |a Receptors, Chimeric Antigen: genetics |2 MeSH |
| 650 | _ | 2 | |a Receptors, Antigen, T-Cell: immunology |2 MeSH |
| 650 | _ | 2 | |a Receptors, Antigen, T-Cell: genetics |2 MeSH |
| 650 | _ | 2 | |a Repressor Proteins: immunology |2 MeSH |
| 650 | _ | 2 | |a Repressor Proteins: genetics |2 MeSH |
| 650 | _ | 2 | |a CD8-Positive T-Lymphocytes: immunology |2 MeSH |
| 650 | _ | 2 | |a Killer Cells, Natural: immunology |2 MeSH |
| 650 | _ | 2 | |a Human papillomavirus 16: immunology |2 MeSH |
| 650 | _ | 2 | |a Human papillomavirus 16: genetics |2 MeSH |
| 650 | _ | 2 | |a Cytotoxicity, Immunologic |2 MeSH |
| 650 | _ | 2 | |a Cell Line, Tumor |2 MeSH |
| 700 | 1 | _ | |a Libório-Ramos, Sofia |0 P:(DE-HGF)0 |b 1 |
| 700 | 1 | _ | |a Leifert, Lena |0 P:(DE-He78)22cadd1a84ded1078feece66c8664d59 |b 2 |
| 700 | 1 | _ | |a Schönfelder, Bruno |0 P:(DE-He78)af9892a34bf8a8a9cf0e7a11a8617645 |b 3 |u dkfz |
| 700 | 1 | _ | |a Vlodavsky, Israel |b 4 |
| 700 | 1 | _ | |a Cid-Arregui, Angel |0 P:(DE-He78)a30064f6b2d9ab959d35315d7668c091 |b 5 |e Last author |u dkfz |
| 773 | _ | _ | |a 10.1002/jmv.29630 |g Vol. 96, no. 5, p. e29630 |0 PERI:(DE-600)1475090-9 |n 5 |p e29630 |t Journal of medical virology |v 96 |y 2024 |x 0146-6615 |
| 856 | 4 | _ | |u https://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 |
| 856 | 4 | _ | |u https://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 |x pdfa |
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