{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["11(44)"],"submitter":["Mortensen MR"],"pubmed_abstract":["There is a growing interest in the antibody-based delivery of cytokines to the tumor environment as a means to boost the anti-cancer activity of tumor-resident T cells and NK cells. Here, we describe the expression and characterization of fusion proteins, featuring the L19 antibody (specific to the alternatively-spliced EDB domain of fibronectin) and an engineered cytokine with interleukin-2 and interleukin-15 properties. The cytokine moiety was fused either at the N-terminal or at the C-terminal extremity and both fusion proteins showed a selective tumor accumulation in a quantitative biodistribution experiment. The N-terminal fusion inhibited tumor growth in immunocompetent mice bearing F9 carcinomas or WEHI-164 sarcomas when used as single agent. The anticancer activity was compared to the one of the same cytokine payload used as recombinant protein or fused to an anti-hen egg lysozyme antibody, serving as negative control of irrelevant specificity in the mouse. These results indicate that the antibody-based delivery of engineered cytokines to the tumor neovasculature may mediate a potent anticancer activity."],"journal":["Oncotarget"],"pagination":["3972-3983"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7646832"],"repository":["biostudies-literature"],"pubmed_title":["Targeting an engineered cytokine with interleukin-2 and interleukin-15 activity to the neovasculature of solid tumors."],"pmcid":["PMC7646832"],"pubmed_authors":["Mortensen MR","Bertolini M","Mock J","Neri D","Stringhini M","Catalano M"],"additional_accession":[]},"is_claimable":false,"name":"Targeting an engineered cytokine with interleukin-2 and interleukin-15 activity to the neovasculature of solid tumors.","description":"There is a growing interest in the antibody-based delivery of cytokines to the tumor environment as a means to boost the anti-cancer activity of tumor-resident T cells and NK cells. Here, we describe the expression and characterization of fusion proteins, featuring the L19 antibody (specific to the alternatively-spliced EDB domain of fibronectin) and an engineered cytokine with interleukin-2 and interleukin-15 properties. The cytokine moiety was fused either at the N-terminal or at the C-terminal extremity and both fusion proteins showed a selective tumor accumulation in a quantitative biodistribution experiment. The N-terminal fusion inhibited tumor growth in immunocompetent mice bearing F9 carcinomas or WEHI-164 sarcomas when used as single agent. The anticancer activity was compared to the one of the same cytokine payload used as recombinant protein or fused to an anti-hen egg lysozyme antibody, serving as negative control of irrelevant specificity in the mouse. These results indicate that the antibody-based delivery of engineered cytokines to the tumor neovasculature may mediate a potent anticancer activity.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Nov","modification":"2024-11-06T20:32:45.823Z","creation":"2020-11-22T09:40:50Z"},"accession":"S-EPMC7646832","cross_references":{"pubmed":["33216834"],"doi":["10.18632/oncotarget.27772"]}}