Anti-cocaine monoclonal antibody 4C6 (mAb 4C6)

Antibody 4C6 is a high-affinity monoclonal antibody (mAb) specifically developed as a therapeutic agent for the treatment of cocaine addiction and toxicity. The '4C6 Fab combining site' refers to the antigen-binding region of the antibody's fragment antigen-binding (Fab) portion, which has been extensively characterized through X-ray crystallography to understand its molecular recognition of the cocaine molecule (Larsen et al., 2001). By binding cocaine in the systemic circulation with nanomolar affinity, mAb 4C6 acts as a 'peripheral sink,' effectively sequestering the drug and preventing it from crossing the blood-brain barrier (Larsen et al., 2004). This pharmacokinetic approach neutralizes the psychoactive and reinforcing effects of cocaine by blocking its access to dopamine transporters in the central nervous system. While mAb 4C6 represents a promising immunotherapeutic strategy, its clinical application faces challenges such as the requirement for high protein doses to match drug intake and the potential for immunogenicity (Ballester et al., 2015). Structural insights from the 4C6 combining site have also facilitated the engineering of catalytic antibodies capable of degrading cocaine into inactive metabolites.

Other names

4C6Cocaine-binding antibody 4C64C6 FabMonoclonal antibody 4C6

Pharmacokinetic antagonism via sequestration of cocaine in the peripheral circulation, preventing its passage across the blood-brain barrier.