Effect of an Anti‐Cocaine Monoclonal Antibody on Body Weights in Self‐Administering Rats

Abstract

A recombinant humanized anti‐cocaine monoclonal antibody (mAb), h2E2 is intended as an immunotherapy for cocaine abuse. This mAb sequesters cocaine in the plasma and inhibits cocaine entry into the brain in rats. h2E2 also increased the cocaine priming threshold in rats indicating that it could reduce the probability of cocaine‐induced relapse in cocaine addicts. However, once cocaine self‐administration was reinstated, h2E2 caused an increase in cocaine consumption in rats. It is possible that the increase in cocaine consumption and the increase in peripheral cocaine concentration in the presence of a foreign protein may be sufficient to induce cardiovascular or other peripherally‐mediated toxicity. Furthermore, multiple treatments with h2E2 will be required clinically and this could provoke toxic immune responses. As the loss of body weight of rats represents a standard indicator of animal health and an FDA‐sanctioned measure of drug toxicity, the effects of a repeated treatment with h2E2 on rat's body weights during cocaine self‐administration were investigated. Rats trained to self‐administer cocaine were infused with h2E2 (120 mg/kg) i.v. Body weights were measured 6 days a week over a 3‐week baseline period, 5 weeks after the first h2E2 infusion and over 5 weeks after the second. No significant weight loss was observed despite an initial moderate increase in cocaine consumption after each h2E2 treatment. There was no evidence that the increase in cocaine consumption in the case of relapse or repeated treatments with h2E2 would represent a safety concern during the treatment of cocaine abusers. Supported by NIH DP1DA031386.