Studies towards the improvement of an anti-cocaine monoclonal antibody for treatment of acute overdose

Bioorg Med Chem Lett. 2016 Oct 15;26(20):5078-5081. doi: 10.1016/j.bmcl.2016.08.081. Epub 2016 Aug 25.

Abstract

There is currently no clinically-approved antidote for cocaine overdose. Efforts to develop a therapy via passive immunization have resulted in a human monoclonal antibody, GNCgzk, with a high affinity for cocaine (Kd=0.18nM). Efforts to improve the production of antibody manifolds based on this antibody are disclosed. The engineering of an HRV 3C protease cleavage site into the GNCgzk IgG has allowed for increased production of a F(ab')2 with a 20% superior capacity to reduce mortality for cocaine overdose in mice.

Keywords: Cocaine; Cocaine overdose; Drugs of abuse; Monoclonal antibody; scFv-Fc.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Disease
  • Animals
  • Antibodies, Monoclonal / immunology*
  • Cocaine / immunology*
  • Drug Overdose / therapy*
  • Half-Life
  • Male
  • Mice

Substances

  • Antibodies, Monoclonal
  • Cocaine