{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Avanzi MP"],"funding":["Carson Family Charitable Trust","Canada Club of New York","Memorial Sloan Kettering","Kate’s Team","The Experimental Therapeutics Center of Memorial Sloan Kettering Cancer Center","William Lawrence and Blanche Hughes Foundation","NIH","Emerald Foundation","Jake Wetchler Foundation","NCI NIH HHS","The Lymphoma Foundation","The Leukemia and Lymphoma Society","NIH HHS"],"pagination":["2130-2141"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5986286"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["23(7)"],"pubmed_abstract":["Chimeric antigen receptor (CAR) T cell therapy has proven clinically beneficial against B cell acute lymphoblastic leukemia and non-Hodgkin's lymphoma. However, suboptimal clinical outcomes have been associated with decreased expansion and persistence of adoptively transferred CAR T cells, antigen-negative relapses, and impairment by an immunosuppressive tumor microenvironment. Improvements in CAR T cell design are required to enhance clinical efficacy, as well as broaden the applicability of this technology. Here, we demonstrate that interleukin-18 (IL-18)-secreting CAR T cells exhibit enhanced in vivo expansion and persistence and significantly increase long-term survival in syngeneic mouse models of both hematological and solid malignancies. In addition, we demonstrate that IL-18-secreting CAR T cells are capable of modulating the tumor microenvironment, as well as enhancing an effective endogenous anti-tumor immune response. IL-18-secreting CAR T cells represent a promising strategy to enhance the clinical outcomes of adoptive T cell therapy."],"journal":["Cell reports"],"pubmed_title":["Engineered Tumor-Targeted T Cells Mediate Enhanced Anti-Tumor Efficacy Both Directly and through Activation of the Endogenous Immune System."],"pmcid":["PMC5986286"],"funding_grant_id":["T32 CA009207","P01CA23766","P01CA059350","P01CA00878","R25 CA020449","R01CA55349","DP5 OD023056","P30 CA008748","R01CA138738-05","P50 CA192937-02","P50 CA192937","P01 CA190174","P01 CA059350","P01 CA023766","5T32-CA009207-38","K12 CA184746","DP5OD023056","R01 CA138738","P01CA190174-03"],"pubmed_authors":["Avanzi MP","Li X","van Leeuwen DG","Park H","Brentjens RJ","Wijewarnasuriya DP","Daniyan AF","Yeku O","Purdon TJ","Cheung K","Spitzer MH"],"additional_accession":[]},"is_claimable":false,"name":"Engineered Tumor-Targeted T Cells Mediate Enhanced Anti-Tumor Efficacy Both Directly and through Activation of the Endogenous Immune System.","description":"Chimeric antigen receptor (CAR) T cell therapy has proven clinically beneficial against B cell acute lymphoblastic leukemia and non-Hodgkin's lymphoma. However, suboptimal clinical outcomes have been associated with decreased expansion and persistence of adoptively transferred CAR T cells, antigen-negative relapses, and impairment by an immunosuppressive tumor microenvironment. Improvements in CAR T cell design are required to enhance clinical efficacy, as well as broaden the applicability of this technology. Here, we demonstrate that interleukin-18 (IL-18)-secreting CAR T cells exhibit enhanced in vivo expansion and persistence and significantly increase long-term survival in syngeneic mouse models of both hematological and solid malignancies. In addition, we demonstrate that IL-18-secreting CAR T cells are capable of modulating the tumor microenvironment, as well as enhancing an effective endogenous anti-tumor immune response. IL-18-secreting CAR T cells represent a promising strategy to enhance the clinical outcomes of adoptive T cell therapy.","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 May","modification":"2026-05-03T11:54:32.675Z","creation":"2019-03-26T23:39:56Z"},"accession":"S-EPMC5986286","cross_references":{"pubmed":["29768210"],"doi":["10.1016/j.celrep.2018.04.051"]}}