# Immunotherapy to Counteract Lethal Doses of Carfentanil

> **NIH NIH U01** · SCRIPPS RESEARCH INSTITUTE, THE · 2021 · $516,902

## Abstract

This proposal is in response to PAR-16-330: “Countermeasures Against Chemical Threats
(CounterACT): Identification of Therapeutic Lead Compounds” and incorporates the development of
monoclonal antibody (mAb) therapy as a solution for acute exposure to the potent synthetic opioid threat,
carfentanil. Beginning in 1979, the illicit synthesis of drugs was elevated to an extraordinarily sophisticated
level. A number of overdose victims' deaths were attributed to heroin, however, seized samples contained no
heroin, rather the victims were inadvertently buying “China White” (i.e., α-methylfentanyl). The fentanyls are a
large family of synthetic analgesics that possess all the properties of the opiates, except they are 100-10,000
times more potent than morphine. Reasons for fentanyl resurfacing are tied to a decline in heroin purity, a need
to increase potency and cost-efficient preparation. Designer fentanyl's can be synthesized at a single location
and because of their potency; a single gram could be formulated (cut) into many thousand, perhaps millions of
doses. Preventing the distribution of such small amounts of a pure drug is exceedingly difficult. Thus, while
drug control efforts will need to continue, so will efforts to treat synthetic psychoactive drug (SPD) abuse. One
(SPD) analogue, carfentanil, is of particular concern because of its extreme potency (10,000 times that of
morphine). It has no therapeutic use in humans, posing a significant mortality risk for opioid users. Another
issue arises from the persistence of carfentanil in the body; the half-life of the drug exceeds naloxone, requiring
multiple infusions of naloxone over time and careful monitoring or else results in re-narcotization. An
aerosolized mixture of carfentanil and remifentanil was used as a chemical warfare agent in Russia, resulting
in 170 civilian deaths in 2002. A promising therapeutic strategy for attenuating the effects of SPDs can be
found in antibody vaccine hapten conjugate. Indeed this strategy has been successfully used against cocaine,
nicotine and methamphetamine. Accordingly, we plan to investigate various antibody manifolds stemming from
these hapten bioconjugates including catalytic antibodies; importantly each unique antibody manifold may
prove more effective than naloxone due drug catabolism and a tunable half-life. We will take two approaches,
active and passive vaccine strategies, to counter this dangerous drug, however, both will be grounded upon
unique hapten design that will be critical in producing antibodies with tight binding and selective specificity.
Antibodies from the latter will come via active vaccination in transgenic OmniRats, and will use a selection
process wherein human antibodies will be secured through unique carfentanil-tagged fluorophore coupled with
fluorescent-activated cell sorting and analysis. Finally, a metric will be needed to judge the value of both types
of vaccines for treating carfentanil's physiological processes; we will...

## Key facts

- **NIH application ID:** 10135036
- **Project number:** 5U01DA046323-03
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Kim Janda
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $516,902
- **Award type:** 5
- **Project period:** 2019-02-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135036

## Citation

> US National Institutes of Health, RePORTER application 10135036, Immunotherapy to Counteract Lethal Doses of Carfentanil (5U01DA046323-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10135036. Licensed CC0.

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