Biologics to treat substance use disorders: Current status and new directions

Abstract

Biologics (vaccines, monoclonal antibodies (mAb), and genetically modified enzymes) offer a promising class of therapeutics to treat substance use disorders (SUD) involving abuse of opioids and stimulants such as nicotine, cocaine, and methamphetamine. In contrast to small molecule medications targeting brain receptors, biologics for SUD are larger molecules that do not cross the blood-brain barrier (BBB), but target the drug itself, preventing its distribution to the brain and blunting its effects on the central nervous system (CNS). Active and passive immunization approaches rely on antibodies (Ab) that bind drugs of abuse in serum and block their distribution to the brain, preventing the rewarding effects of drugs and addiction-related behaviors. Alternatives to vaccines and anti-drug mAb are genetically engineered human or bacterial enzymes that metabolize drugs of abuse, lowering the concentration of free active drug. Pre-clinical and clinical data support development of effective biologics for SUD.

Keywords: B cell; T cell; adjuvants; antibodies; biologics; delivery; drug addiction; drug development; materials; nanoparticles; screening; vaccines.

Figure 1.

The frequency of hapten-specific B cells in blood predicts vaccine efficacy. Pre- and post-vaccination 6OXY-specific B cells were analyzed in 0.2 ml of blood collected before and after immunization with either 6OXY-KLH or KLH. Balb/c mice were immunized on days 0, 14 and 28, and challenged with 2.25 mg/kg oxycodone a week after the third immunization to measure the effect of immunization on oxycodone distribution. A) Immunization reduced distribution of oxycodone to the brain. Data are mean ± SEM. B) Early serum IgG antibody titers correlated to subsequent blockage of oxycodone distribution to the brain. C) The frequency of 6OXY-specific IgM^high B cells prior to immunization correlated with vaccine efficacy in the 6OXY-KLH group. D) Increased frequency of 6OXY-specific IgM^high B cells 14 days after the first immunization correlated to greater vaccine efficacy on oxycodone distribution to the brain. Frequencies are the % of total lymphocytes in the bound fraction after positive enrichment of blood. Data include 3 independent experiments with a total of n = 12 mice each group. *** p < 0.001 compared to KLH control. Copyright 2015. The American Association of Immunologists, Inc.