Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0WRMGX
ADC Name
Anti-TNF ADC 134
Synonyms
Anti-TNF-ADC-134
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Organization
AbbVie, Inc.
Drug Status
Investigative
Indication
In total 1 Indication(s)
Rheumatoid arthritis [ICD11:FA20]
Investigative
Drug-to-Antibody Ratio
4
Structure
Antibody Name
Anti-TNF mAb alpha-TNF
  Antibody Info 
Antigen Name
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A)
  Antigen Info 
Payload Name
GRM cpd 64
  Payload Info 
Therapeutic Target
Glucocorticoid receptor (NR3C1)
  Target Info 
Linker Name
MP-Ala-Ala
  Linker Info 
Conjugate Type
The free sulfhydryl group obtained by the reduction of interchain cysteine is site-specific conjugated with maleimide, michael addition reaction, followed by incubation at basic ph to hydrolyze-open the maleimide ring.
General Information of The Activity Data Related to This ADC
Obtained from the Model Organism Data
Click To Hide/Show 6 Activity Data Related to This Level
Standard Type Value Units Animal Model (No. of PDX)
P1NP inhibition 
25
%
Acute contact hypersensitivity (CHS) model
P1NP inhibition 
58
%
Acute contact hypersensitivity (CHS) model
Ear swelling inhibition 
72
%
Fluorescein isothiocyanate (FITC)-induced CHS model
Ear swelling inhibition 
94
%
Fluorescein isothiocyanate (FITC)-induced CHS model
Corticosterone inhibition 
36
%
Acute contact hypersensitivity (CHS) model
Corticosterone inhibition 
74
%
Acute contact hypersensitivity (CHS) model
Revealed Based on the Cell Line Data
Click To Hide/Show 2 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Half Maximal Effective Concentration (EC50) 
0.8
ng/mL
K-562 cells (TNF expression)
Chronic myelogenous leukemia
Half Maximal Effective Concentration (EC50) 
10.7
ug/mL
K-562 cells
Chronic myelogenous leukemia
Full List of Activity Data of This Antibody-drug Conjugate
Obtained from the Model Organism Data
Click To Hide/Show 6 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data P1NP inhibition 25.00% Positive TNF expression (TNF+++/++)
Method Description
In an acute in vivo model of contact hypersensitivity (CHS) mice were sensitized with fluorescein isothiocyanate (FITC) on the abdomen and challenged 6 days later with FITC on the ear,which resulted in an increase in ear swelling that was measured 24 h postchallenge. Anti-mTNF GRM ADCs were dosed at either 3 mg/kg once prior to FITC sensitization. Mice were challenged with adrenocorticotropic hormone (ACTH) 72 h following ADC dosing and plasma was collected 30 min later to assess P1NP level.

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In Vivo Model Acute contact hypersensitivity (CHS) model
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data P1NP inhibition 58.00% Positive TNF expression (TNF+++/++)
Method Description
In an acute in vivo model of contact hypersensitivity (CHS) mice were sensitized with fluorescein isothiocyanate (FITC) on the abdomen and challenged 6 days later with FITC on the ear,which resulted in an increase in ear swelling that was measured 24 h postchallenge. Anti-mTNF GRM ADCs were dosed at either 10 mg/kg once prior to FITC sensitization. Mice were challenged with adrenocorticotropic hormone (ACTH) 72 h following ADC dosing and plasma was collected 30 min later to assess P1NP level.

   Click to Show/Hide
In Vivo Model Acute contact hypersensitivity (CHS) model
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Ear swelling inhibition 72.00% Positive TNF expression (TNF+++/++)
Method Description
In an acute in vivo model of contact hypersensitivity (CHS) mice were sensitized with fluorescein isothiocyanate (FITC) on the abdomen and challenged 6 days later with FITC on the ear,which resulted in an increase in ear swelling that was measured 24 h postchallenge. Anti-mTNF GRM ADCs were dosed at either 3 mg/kg once prior to FITC sensitization.
In Vivo Model Fluorescein isothiocyanate (FITC)-induced CHS model
Experiment 4 Reporting the Activity Date of This ADC [1]
Efficacy Data Ear swelling inhibition 94.00% Positive TNF expression (TNF+++/++)
Method Description
In an acute in vivo model of contact hypersensitivity (CHS) mice were sensitized with fluorescein isothiocyanate (FITC) on the abdomen and challenged 6 days later with FITC on the ear,which resulted in an increase in ear swelling that was measured 24 h postchallenge. Anti-mTNF GRM ADCs were dosed at either 10 mg/kg once prior to FITC sensitization.
In Vivo Model Fluorescein isothiocyanate (FITC)-induced CHS model
Experiment 5 Reporting the Activity Date of This ADC [1]
Efficacy Data Corticosterone inhibition 36.00% Positive TNF expression (TNF+++/++)
Method Description
In an acute in vivo model of contact hypersensitivity (CHS) mice were sensitized with fluorescein isothiocyanate (FITC) on the abdomen and challenged 6 days later with FITC on the ear,which resulted in an increase in ear swelling that was measured 24 h postchallenge. Anti-mTNF GRM ADCs were dosed at either 3 mg/kg once prior to FITC sensitization. Mice were challenged with adrenocorticotropic hormone (ACTH) 72 h following ADC dosing and plasma was collected 30 min later to assess corticosterone level.

   Click to Show/Hide
In Vivo Model Acute contact hypersensitivity (CHS) model
Experiment 6 Reporting the Activity Date of This ADC [1]
Efficacy Data Corticosterone inhibition 74.00% Positive TNF expression (TNF+++/++)
Method Description
In an acute in vivo model of contact hypersensitivity (CHS) mice were sensitized with fluorescein isothiocyanate (FITC) on the abdomen and challenged 6 days later with FITC on the ear,which resulted in an increase in ear swelling that was measured 24 h postchallenge. Anti-mTNF GRM ADCs were dosed at either 10 mg/kg once prior to FITC sensitization. Mice were challenged with adrenocorticotropic hormone (ACTH) 72 h following ADC dosing and plasma was collected 30 min later to assess corticosterone level.

   Click to Show/Hide
In Vivo Model Acute contact hypersensitivity (CHS) model
Revealed Based on the Cell Line Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Effective Concentration (EC50) 0.80 ng/mL Positive TNF expression (TNF+++/++)
Method Description
All the DAR purified ADCs were screened in both the TNF-expressing and wild-type K562 GRE reporter cell assay to confirm that their activity was consistent with ADCs having heterogeneous average DAR.
In Vitro Model Chronic myelogenous leukemia K-562 cells (TNF expression) CVCL_0004
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Effective Concentration (EC50) 10.70 ug/mL Negative TNF expression (TNF-)
Method Description
All the DAR purified ADCs were screened in both the TNF-expressing and wild-type K562 GRE reporter cell assay to confirm that their activity was consistent with ADCs having heterogeneous average DAR.
In Vitro Model Chronic myelogenous leukemia K-562 cells CVCL_0004
References
Ref 1 Discovery of ABBV-3373, an Anti-TNF Glucocorticoid Receptor Modulator Immunology Antibody Drug Conjugate. J Med Chem. 2022 Dec 8;65(23):15893-15934.

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