% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{QuirosFernandez:289779, author = {I. Quiros-Fernandez$^*$ and S. Libório-Ramos$^*$ and L. Leifert$^*$ and B. Schönfelder$^*$ and I. Vlodavsky and A. Cid-Arregui$^*$}, title = {{D}ual {T} cell receptor/chimeric antigen receptor engineered {NK}-92 cells targeting the {HPV}16 {E}6 oncoprotein and the tumor-associated antigen {L}1{CAM} exhibit enhanced cytotoxicity and specificity against tumor cells.}, journal = {Journal of medical virology}, volume = {96}, number = {5}, issn = {0146-6615}, address = {Bognor Regis [u.a.]}, publisher = {Wiley}, reportid = {DKFZ-2024-00858}, pages = {e29630}, year = {2024}, note = {#EA:D122#LA:D122#}, abstract = {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.}, keywords = {Humans / Oncogene Proteins, Viral: immunology / Oncogene Proteins, Viral: genetics / Receptors, Chimeric Antigen: immunology / Receptors, Chimeric Antigen: genetics / Receptors, Antigen, T-Cell: immunology / Receptors, Antigen, T-Cell: genetics / Repressor Proteins: immunology / Repressor Proteins: genetics / CD8-Positive T-Lymphocytes: immunology / Killer Cells, Natural: immunology / Human papillomavirus 16: immunology / Human papillomavirus 16: genetics / Cytotoxicity, Immunologic / Cell Line, Tumor / CAR (Other) / T cell receptor (Other) / adoptive cell transfer (Other) / cell therapy (Other) / cervical cancer (Other) / chimeric antigen receptor (Other) / human papillomavirus (Other) / immunotherapy (Other) / Oncogene Proteins, Viral (NLM Chemicals) / E6 protein, Human papillomavirus type 16 (NLM Chemicals) / Receptors, Chimeric Antigen (NLM Chemicals) / Receptors, Antigen, T-Cell (NLM Chemicals) / Repressor Proteins (NLM Chemicals)}, cin = {D122}, ddc = {610}, cid = {I:(DE-He78)D122-20160331}, pnm = {314 - Immunologie und Krebs (POF4-314)}, pid = {G:(DE-HGF)POF4-314}, typ = {PUB:(DE-HGF)16}, pubmed = {pmid:38659368}, doi = {10.1002/jmv.29630}, url = {https://inrepo02.dkfz.de/record/289779}, }