Anti-OX40 (CD134) administration to nonhuman primates: Immunostimulatory effects and toxicokinetic study

Andrew D. Weinberg, Colin Thalhofer, Nick Morris, Joshua M. Walker, Donald Seiss, Scott Wong, Michael K. Axthelm, Louis J. Picker, Walter J. Urba

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

The immune-stimulatory properties of anti-CD134 (OX40) antibodies have been well documented in rodents, including their ability to enhance antitumor immunity. In this study, an anti-OX40 antibody (Ab) known to costimulate monkey T cells in vitro, was infused into rhesus macaque monkeys during immunization with the simian immunodeficiency virus protein, gp130. The draining lymph nodes from immunized monkeys treated with anti-OX40 were enlarged compared with immunized monkeys injected with mouse Ig. Anti-OX40-treated monkeys had increased gp130-specific Ab titers, and increased long-lived T-cell responses, compared with controls. There were no overt signs of toxicity in the anti-OX40-treated monkeys. The encouraging immune-stimulatory effects led to the good manufacturing practice production of an anti-OX40 Ab for clinical trials in cancer patients. A detailed toxicology study was performed with anti-OX40 in nonhuman primates. Three groups of 8 monkeys received anti-OX40 at 1 of 3 dose levels (0.4, 2.0, and 10 mg/kg) and a control group received saline. No clinical toxicity was observed, but acute splenomegaly and enlarged gut-associated lymph nodes were observed in the anti-OX40-treated animals; splenomegaly and lymphadenopathy resolved by day 28. These studies demonstrate the immune-stimulatory properties and safety of anti-OX40 in primates and provide a strong scientific rationale to pursue clinical trials in humans.

Original languageEnglish (US)
Pages (from-to)575-585
Number of pages11
JournalJournal of Immunotherapy
Volume29
Issue number6
DOIs
StatePublished - Nov 1 2006

Keywords

  • Costimulation
  • Immunotherapy
  • T cells
  • TNF receptor family member

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

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