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 Axthelm, Louis Picker, Walter J. Urba

Research output: Contribution to journalArticle

41 Citations (Scopus)

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 2006

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Primates
Haplorhini
Splenomegaly
Macaca mulatta
Anti-Idiotypic Antibodies
Lymph Nodes
Clinical Trials
T-Lymphocytes
Antibodies
Toxicology
Toxicokinetics
Immunity
Rodentia
Immunization
Safety
Control Groups
Neoplasms
Proteins

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

Cite this

Anti-OX40 (CD134) administration to nonhuman primates : Immunostimulatory effects and toxicokinetic study. / Weinberg, Andrew D.; Thalhofer, Colin; Morris, Nick; Walker, Joshua M.; Seiss, Donald; Wong, Scott; Axthelm, Michael; Picker, Louis; Urba, Walter J.

In: Journal of Immunotherapy, Vol. 29, No. 6, 11.2006, p. 575-585.

Research output: Contribution to journalArticle

Weinberg, Andrew D. ; Thalhofer, Colin ; Morris, Nick ; Walker, Joshua M. ; Seiss, Donald ; Wong, Scott ; Axthelm, Michael ; Picker, Louis ; Urba, Walter J. / Anti-OX40 (CD134) administration to nonhuman primates : Immunostimulatory effects and toxicokinetic study. In: Journal of Immunotherapy. 2006 ; Vol. 29, No. 6. pp. 575-585.
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