Engagement of the OX-40 receptor in vivo enhances antitumor immunity

Andrew D. Weinberg, Martin Muy Rivera, Rodney Prell, Arden Morris, Trygg Ramstad, John T. Vetto, Walter J. Urba, Gregory Alvord, Campbell Bunce, John Shields

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284 Scopus citations

Abstract

The OX-40 receptor (OX-40R), a member of the TNFR family, is primarily expressed on activated CD4+ T lymphocytes. Engagement of the OX-40R, with either OX-40 ligand (OX-40L) or an Ab agonist, delivers a strong costimulatory signal to effector T cells. OX-40R+ T cells isolated from inflammatory lesions in the CNS of animals with experimental autoimmune encephalomyelitis are the cells that respond to autoantigen (myelin basic protein) in vivo. We identified OX-40R+ T cells within primary tumors and tumor-invaded lymph nodes of patients with cancer and hypothesized that they are the tumor-Ag-specific T cells. Therefore, we investigated whether engagement of the OX-40R in vivo during tumor priming would enhance a tumor- specific T cell response. Injection of OX-40L:Ig or anti-OX-40R in vivo during tumor priming resulted in a significant improvement in the percentage of tumor-free survivors (20-55%) in four different murine tumors derived from four separate tissues. This anti-OX-40R effect was dose dependent and accentuated tumor-specific T cell memory. The data suggest that engagement of the OX-40R in vivo augments tumor-specific priming by stimulating/expanding the natural repertoire of the host's tumor-specific CD4+ T cells. The identification of OX-40R+ T cells clustered around human tumor cells in vivo suggests that engagement of the OX-40R may be a practical approach for expanding tumor-reactive T cells and thereby a method to improve tumor immunotherapy in patients with cancer.

Original languageEnglish (US)
Pages (from-to)2160-2169
Number of pages10
JournalJournal of Immunology
Volume164
Issue number4
DOIs
StatePublished - Feb 15 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Weinberg, A. D., Rivera, M. M., Prell, R., Morris, A., Ramstad, T., Vetto, J. T., Urba, W. J., Alvord, G., Bunce, C., & Shields, J. (2000). Engagement of the OX-40 receptor in vivo enhances antitumor immunity. Journal of Immunology, 164(4), 2160-2169. https://doi.org/10.4049/jimmunol.164.4.2160