<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "BiTE-armed oncolytic measles viruses for cancer immunovirotherapy"^^ . "Attenuated measles virus (MV) vaccine strains preferentially infect, replicate in and thus\r\ndestruct cancerous cells. In recent years, it has become evident that therapeutic success of\r\noncolytic virotherapy largely depends on the modulation of the immune system. MV-mediated\r\noncolysis induces an immunogenic cell death (ICD), which provides the basis to enhance or\r\nreinitiate a sustained antitumor immune response. In clinical testing, salvage therapy with\r\noncolytic MV has led to complete tumor resolutions, demonstrating its therapeutic potential.\r\nHowever, extensive therapeutic efficacy is limited to a minority of patients. Thus, efforts are\r\nput into preclinical research to generate more potent MV vectors.\r\nMany strategies in cancer immunotherapy aim to augment T cell responses against tumor cells.\r\nBispecific T cell engagers (BiTEs) simultaneously engage T cells and tumor cells. BiTEmediated\r\nT cell engagement activates the engaged T cell and specifically directs its cytotoxic\r\npotential towards the crosslinked tumor cell. BiTE therapy has achieved compelling clinical\r\nsuccess in the treatment of B cell malignancies. However, BiTEs have failed to demonstrate\r\nefficacy against solid tumors so far. Moreover, short terminal half-life of BiTEs requires\r\ncontinuous intravenous infusion and systemic administration of BiTEs can cause severe or even\r\nfatal side effects.\r\nWe hypothesize that tumor-targeted expression of BiTEs by oncolytic MV enhances therapeutic\r\nefficacy, as compared to either monotherapy alone. Furthermore, we hypothesize that tumorrestricted\r\nBiTE-expression reduces systemic exposure to BiTEs and thus increases safety of\r\nBiTE therapy. To test these hypotheses, MVs encoding BiTEs were generated (MV-BiTE).\r\nMV-BiTE vectors were characterized in vitro in terms of replication kinetics, oncolytic activity\r\nand BiTE expression. BiTEs produced by MV-BiTE-infected cells were purified to evaluate\r\nbinding specificity and BiTE-mediated T cell cytotoxicity in vitro. Therapeutic efficacy of MVBiTE\r\nin terms of survival was demonstrated using syngeneic and xenogeneic tumor models.\r\nFor all studies, no signs of MV-BiTE-related toxicities were observed and BiTE plasma levels\r\nof MV-BiTE-treated mice remained below detection limit.\r\nConclusively, tumor-targeted expression of BiTEs by oncolytic MV is feasible and prevented\r\nsystemic exposure to BiTEs. Moreover, MV-BiTE treatment demonstrated therapeutic efficacy\r\nin different models of solid tumors in vivo. The MV-BiTE constructs constitute a modular\r\nvector platform that can be adapted to target any tumor antigen of choice. Thus, MV-BiTE\r\ntherapy represents a promising approach for individualized cancer immunovirotherapy."^^ . "2018" . . . . . . . "Tobias"^^ . "Speck"^^ . "Tobias Speck"^^ . . . . . . "BiTE-armed oncolytic measles viruses for cancer immunovirotherapy (PDF)"^^ . . . "2017-12-14 - Speck, Tobias - Dissertation_final.pdf"^^ . . . "BiTE-armed oncolytic measles viruses for cancer immunovirotherapy (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "BiTE-armed oncolytic measles viruses for cancer immunovirotherapy (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "BiTE-armed oncolytic measles viruses for cancer immunovirotherapy (Other)"^^ . . . . . . "preview.jpg"^^ . . . "BiTE-armed oncolytic measles viruses for cancer immunovirotherapy (Other)"^^ . . . . . . "medium.jpg"^^ . . . "BiTE-armed oncolytic measles viruses for cancer immunovirotherapy (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #24228 \n\nBiTE-armed oncolytic measles viruses for cancer immunovirotherapy\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .