Reducing toxicity of 4-1BB costimulation: targeting 4-1BB ligands to the tumor stroma with bi-specific aptamer conjugates

B Schrand; A Berezhnoy; R Brenneman; A Williams; A Levay; E Gilboa

doi:10.4161/21624011.2014.970918

Reducing toxicity of 4-1BB costimulation: targeting 4-1BB ligands to the tumor stroma with bi-specific aptamer conjugates

Oncoimmunology. 2015 Jan 9;4(3):e970918. doi: 10.4161/21624011.2014.970918. eCollection 2015 Mar.

Authors

B Schrand¹, A Berezhnoy¹, R Brenneman¹, A Williams², A Levay¹, E Gilboa¹

Affiliations

¹ Department of Microbiology & Immunology; Dodson Interdisciplinary Immunotherapy Institute; Sylvester Comprehensive Cancer Center; University of Miami ; Miami, FL, USA.
² Department of Pathology; Miller School of Medicine; University of Miami ; Miami, FL, USA.

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.

Keywords: 4–1BB; VEGF; autoimmune pathology; cancer immunotherapy; immune stimulation; tumor stroma; tumor targeting.