Secondary Logo

Institutional members access full text with Ovid®

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 K.; Picker, Louis J.; Urba, Walter J.*

doi: 10.1097/01.cji.0000211319.00031.fc
Basic Studies
Buy

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.

*Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, 5F40, Portland, OR

Vaccine and Gene Therapy Institute and Division of Pathobiology and Immunology, Oregon National Primate Research Center, Oregon Health & Science University, West Campus, 505 NW 185th Beaverton, OR

Reprints: Andrew D. Weinberg, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, 5F40, Portland, OR 97213 (e-mail: andrew.weinberg@providence.org).

Received for publication March 17, 2006; accepted April 13 2006

This work was supported by NIH Grant CA102577-01, CA101690-02, DOD Grant DAMD 17-03-01-0093, and the Providence Medical Center Foundation for ADW.

Financial Disclosure: Dr Weinberg has declared that Providence Medical Center has filed a patent to use anti-OX40 to augment immunity in humans and Dr Weinberg is the inventor on the patent. The remaining authors have declared there are no financial conflicts of interest related to this work.

© 2006 Lippincott Williams & Wilkins, Inc.