Antibodies targeting human OX40 expand effector T cells and block inducible and natural regulatory T cell function

Kui S. Voo, Laura Bover, Megan L. Harline, Long T. Vien, Valeria Facchinetti, Kazuhiko Arima, Larry W. Kwak, Yong J. Liu

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

Current cancer vaccines induce tumor-specific T cell responses without sustained tumor regression because immunosuppressive elements within the tumor induce exhaustion of effector T cells and infiltration of immune-suppressive regulatory T cells (Tregs). Therefore, much effort has been made to generate agonistic Abs targeting members of the TNFR superfamily, such as OX 40, 4-1BB, and GITR, expressed on effector T cells and Tregs, to reinvigorate T cell effector function and block Treg-suppressive function. In this article, we describe the development of a panel of anti-human OX40 agonistic mouse mAbs that could promote effector CD4+ and CD8+ T cell proliferation, inhibit the induction of CD4+ IL-10 -producing type 1 regulatory T cells, inhibit the expansion of ICOS+IL-10+ Tregs, inhibit TGF-β-induced FOXP3 expression on naive CD4+ T cells, and block natural Treg-suppressive function. We humanized two anti-human OX40 mAb clones, and they retained the potency of their parental clones. These Abs should provide broad opportunities for potential combination therapy to treat a wide realm of cancers and preventative vaccines against infectious diseases.

Original languageEnglish (US)
Pages (from-to)3641-3650
Number of pages10
JournalJournal of Immunology
Volume191
Issue number7
DOIs
StatePublished - Oct 1 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

MD Anderson CCSG core facilities

  • Monoclonal Antibody Facility
  • Flow Cytometry and Cellular Imaging Facility

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