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

Brett Schrand, A. Berezhnoy, R. Brenneman, A. Williams, A. Levay, Eli Gilboa

Research output: Contribution to journalArticle

13 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1-3
Number of pages3
JournalOncoImmunology
Volume4
Issue number3
DOIs
StatePublished - 2015

Keywords

  • 4–1BB
  • Autoimmune pathology
  • Cancer immunotherapy
  • Immune stimulation
  • Tumor stroma
  • Tumor targeting
  • VEGF

ASJC Scopus subject areas

  • Immunology and Allergy
  • Oncology
  • Immunology

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