title: Reducing toxicity of 4-1BB costimulation: targeting 4-1BB ligands to the tumor stroma with bi-specific aptamer conjugates.
abstract: Systemic administration of immune modulatory antibodies to cancer patients is associated with autoimmune pathologies. We have developed a clinically feasible and broadly applicable approach to limit immune stimulation to disseminated tumor lesions using a bi-specific agonistic 4-1BB oligonucleotide aptamer targeted to a broadly expressed stromal product (e.g., VEGF or osteopontin). The stroma-targeted aptamer conjugates engendered potent antitumor immunity against unrelated tumors and exhibited a superior therapeutic index compared to non-targeted agonistic 4-1BB antibody.
authors.affiliation: Department of Microbiology & Immunology; Dodson Interdisciplinary Immunotherapy Institute; Sylvester Comprehensive Cancer Center; University of Miami ; Miami, FL, USA.
authors.forename: B
authors.initials: B
authors.lastname: Schrand
authors.affiliation: Department of Microbiology & Immunology; Dodson Interdisciplinary Immunotherapy Institute; Sylvester Comprehensive Cancer Center; University of Miami ; Miami, FL, USA.
authors.forename: A
authors.initials: A
authors.lastname: Berezhnoy
authors.affiliation: Department of Microbiology & Immunology; Dodson Interdisciplinary Immunotherapy Institute; Sylvester Comprehensive Cancer Center; University of Miami ; Miami, FL, USA.
authors.forename: R
authors.initials: R
authors.lastname: Brenneman
authors.affiliation: Department of Pathology; Miller School of Medicine; University of Miami ; Miami, FL, USA.
authors.forename: A
authors.initials: A
authors.lastname: Williams
authors.affiliation: Department of Microbiology & Immunology; Dodson Interdisciplinary Immunotherapy Institute; Sylvester Comprehensive Cancer Center; University of Miami ; Miami, FL, USA.
authors.forename: A
authors.initials: A
authors.lastname: Levay
authors.affiliation: Department of Microbiology & Immunology; Dodson Interdisciplinary Immunotherapy Institute; Sylvester Comprehensive Cancer Center; University of Miami ; Miami, FL, USA.
authors.forename: E
authors.initials: E
authors.lastname: Gilboa
keywords: 4–1BB; VEGF; autoimmune pathology; cancer immunotherapy; immune stimulation; tumor stroma; tumor targeting