<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Novel T cell receptors reactive to the HPV16 E6 and E7 oncoproteins and strategy to potentiate their signaling strength using a co-stimulatory chimeric antigen receptor"^^ . "More than 95% of all cervical cancer cases worldwide are caused by high-risk human papillomaviruses (HPV). The transformation and survival of the malignant HPV+ cells depend on the expression of the viral E6 and E7 oncoproteins, which makes them appropriate tumor-specific targets for immunotherapy. However, viral antigen presentation by tumor cells is generally low and limits the efficacy of tumor-reactive CD8+ T cells. In fact, adoptive cell therapies based on tumor-reactive T cell receptors (TCR) have shown limited efficacy as stand-alone treatments against solid tumors. In order to increase the efficacy of adoptive TCR-based immunotherapy of cancers caused by HPV16, a new strategy was devised combining an HPV16-specific TCR with a co-stimulatory chimeric antigen receptor (CAR). \r\nTCRs specific against the HPV16 E6 and E7 proteins were identified from the repertoire of healthy HLA-A2 donors and were characterized in terms of activation and cytotoxic capacity using the TCR-deficient Jurkat J76 cell line, and a novel NK-92-derived cell line capable of inducing TCR-mediated cytotoxicity. An E6-reactive TCR induced potent cytotoxicity towards HPV16+ cancer cell lines, while a TCR, reactive against the E7 protein showed weaker cytotoxicity against the HPV16+ cell lines tested. To enhance the specificity and signaling strength of the NK-92/TCR cells, a co-stimulatory CAR directed against the trophoblast cell surface antigen 2 (TROP2) was designed, carrying exclusively the intracellular domain of the inducible T cell co-stimulator protein (ICOS). NK-92 cells with co-expression of the E7-reactive TCR and the co-stimulatory CAR showed enhanced cytotoxicity against the HPV16+ and TROP2+ cancer cell lines. Overall, the data shows that a co-stimulatory TROP2-CAR can synergize with a tumor-specific TCR in NK-92 cells, enhancing their signaling strength and antigen-specific cytotoxicity. Such combination approach can help improve the efficacy of TCR-based adoptive cell immunotherapies of HPV16+ cancer patients."^^ . "2024" . . . . . . . "Isaac"^^ . "Quirós Fernández"^^ . "Isaac Quirós Fernández"^^ . . . . . . "Novel T cell receptors reactive to the HPV16 E6 and E7 oncoproteins and strategy to potentiate their signaling strength using a co-stimulatory chimeric antigen receptor (PDF)"^^ . . . "Novel T cell receptors reactive to the HPV16 E6 and E7 oncoproteins and strategy to potentiate their signaling strength using a co-stimulatory chimeric antigen receptor (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Novel T cell receptors reactive to the HPV16 E6 and E7 oncoproteins and strategy to potentiate their signaling strength using a co-stimulatory chimeric antigen receptor (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Novel T cell receptors reactive to the HPV16 E6 and E7 oncoproteins and strategy to potentiate their signaling strength using a co-stimulatory chimeric antigen receptor (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Novel T cell receptors reactive to the HPV16 E6 and E7 oncoproteins and strategy to potentiate their signaling strength using a co-stimulatory chimeric antigen receptor (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Novel T cell receptors reactive to the HPV16 E6 and E7 oncoproteins and strategy to potentiate their signaling strength using a co-stimulatory chimeric antigen receptor (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #33900 \n\nNovel T cell receptors reactive to the HPV16 E6 and E7 oncoproteins and strategy to potentiate their signaling strength using a co-stimulatory chimeric antigen receptor\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .