Multivalent RNA Aptamers That Inhibit CTLA-4 and Enhance Tumor Immunity

Sandra Santulli-Marotto, Smita K. Nair, Chris Rusconi, Bruce Sullenger, Eli Gilboa

Research output: Contribution to journalArticle

131 Scopus citations

Abstract

The potency of cancer immunotherapy can be enhanced by administration of high-avidity ligands specific to receptors expressed on T cells. Antibodies or cytokines are the main agents used in such capacity. Antibody-mediated inhibition of cytotoxic T cell antigen-4 (CTLA-4) function in mice augments antitumor immunity and could serve as an important adjunct in cancer immunotherapy. However, antibody-based therapy used in the setting of chronic diseases such as cancer poses significant cost, manufacturing, and regulatory challenges. Here we describe the development of RNA aptamers that bind CTLA-4 with high affinity and specificity. These aptamers inhibit CTLA-4 function in vitro and enhance tumor immunity in mice. Moreover, assembly of the aptamers into tetrameric forms significantly enhances their bioactivity in vitro and in vivo. These results demonstrate that aptamers can be used to manipulate the immune system for therapeutic applications and that multivalent versions of aptamers may be particularly potent agents in vivo.

Original languageEnglish (US)
Pages (from-to)7483-7489
Number of pages7
JournalCancer Research
Volume63
Issue number21
StatePublished - Nov 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Santulli-Marotto, S., Nair, S. K., Rusconi, C., Sullenger, B., & Gilboa, E. (2003). Multivalent RNA Aptamers That Inhibit CTLA-4 and Enhance Tumor Immunity. Cancer Research, 63(21), 7483-7489.