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… - …, 2015 - Taylor & Francis
B Schrand, A Berezhnoy, R Brenneman, A Williams, A Levay, E Gilboa
Oncoimmunology, 2015•Taylor & FrancisSystemic 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 (eg, VEGF or osteopontin). The stroma-targeted aptamer conjugates engendered
potent antitumor immunity against unrelated tumors and exhibited a superior therapeutic …
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 (eg, VEGF or osteopontin). The stroma-targeted aptamer conjugates engendered
potent antitumor immunity against unrelated tumors and exhibited a superior therapeutic …
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.
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