Development of
an Effective Monoclonal Antibody against
Heroin and Its Metabolites Reveals Therapies Have Mistargeted 6‑Monoacetylmorphine
and Morphine over Heroin
The opioid epidemic is a global public health crisis
that has failed
to abate with current pharmaceutical treatments. Moreover, these FDA-approved
drugs possess numerous problems such as adverse side effects, short
half-lives, abuse potential, and recidivism after discontinued use.
An alternative treatment model for opioid use disorders is immunopharmacotherapy,
where antibodies are produced to inhibit illicit substances by sequestering
the drug in the periphery. Immunopharmacotherapeutics against heroin
have engaged both active and passive vaccines targeting heroin’s
metabolites, 6-monoacetylmorphine (6-AM) and morphine, since decades
of research have stated that heroin’s psychoactive and lethal
effects are mainly attributed to these compounds. However, concerted
efforts to develop effective immunopharmacotherapies against heroin
abuse have faced little clinical advancement, suggesting a need for
reassessing drug target selection. To address this issue, four unique
monoclonal antibodies were procured with distinct affinity to either
heroin, 6-AM, or morphine. Examination of these antibodies through in vitro and in vivo tests revealed monoclonal
antibody 11D12 as the optimal therapeutic and provided crucial insights
into the key chemical species to target for blunting heroin’s
psychoactive and lethal effects. These findings offer clarification
into the problematic attempts of therapeutics targeting heroin’s
metabolites and provide a path forward for future heroin immunopharmacotherapy
development