Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ID: DRG0RMJDO)
ADC Name
US11147852B2 5T4-L443C 2.1
Synonyms
5T4-L443C
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Organization
PFIZER INC.
Drug Status
Investigative
Drug-to-Antibody Ratio
2.1
Antibody Name
anti-5T4
  Antibody Info 
Antigen Name
Trophoblast glycoprotein (TPBG)
  Antigen Info 
Payload Name
Undisclosed
Linker Name
Undisclosed
Conjugate Type
Random conjugation through reduced inter-chain cysteines.
Combination Type
McMMAD
2027 Update
General Information of The ADMET Data Related to This ADC
Absorption
Click To Hide/Show 4 Absorption Data Related to This Level
Standard Type Value Units Description Reference
Maximum Observed Concentration (Cmax) 61.3 ug/mL
A study was conducted to determine the pharmacokinetic parameters of human anti-5T4 antibody comprising a wild type IgG1 Fe region and human cys mutant anti-5T4 antibody site specifically conjugated to a payload (ADC) in female nu/nu mice (non tumor bearing) given a single 3 mg/kg IV dose of either 5T4 antibody alone, 5T4-mcM MAD ADC (conventional cys-conjugation) or various 5T4 cys-mutant mcMMAD ADCs.

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 [1]
Area Under the Concentration-Time Curve (AUC) 6220 ug·h/mL
A study was conducted to determine the pharmacokinetic parameters of human anti-5T4 antibody comprising a wild type IgG1 Fe region and human cys mutant anti-5T4 antibody site specifically conjugated to a payload (ADC) in female nu/nu mice (non tumor bearing) given a single 3 mg/kg IV dose of either 5T4 antibody alone, 5T4-mcM MAD ADC (conventional cys-conjugation) or various 5T4 cys-mutant mcMMAD ADCs.

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 [1]
Maximum Observed Concentration (Cmax) 55.8 ug/mL
A study was conducted to determine the pharmacokinetic parameters of human anti-5T4 antibody comprising a wild type IgG1 Fe region and human cys mutant anti-5T4 antibody site specifically conjugated to a payload (ADC) in female nu/nu mice (non tumor bearing) given a single 3 mg/kg IV dose of either 5T4 antibody alone, 5T4-mcM MAD ADC (conventional cys-conjugation) or various 5T4 cys-mutant mcMMAD ADCs.

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 [1]
Area Under the Concentration-Time Curve (AUC) 5220 ug·h/mL
A study was conducted to determine the pharmacokinetic parameters of human anti-5T4 antibody comprising a wild type IgG1 Fe region and human cys mutant anti-5T4 antibody site specifically conjugated to a payload (ADC) in female nu/nu mice (non tumor bearing) given a single 3 mg/kg IV dose of either 5T4 antibody alone, 5T4-mcM MAD ADC (conventional cys-conjugation) or various 5T4 cys-mutant mcMMAD ADCs.

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 [1]
Excretion
Click To Hide/Show 2 Excretion Data Related to This Level
Standard Type Value Units Description Reference
Clearance (CL) 0.52 mL/h/kg
A study was conducted to determine the pharmacokinetic parameters of human anti-5T4 antibody comprising a wild type IgG1 Fe region and human cys mutant anti-5T4 antibody site specifically conjugated to a payload (ADC) in female nu/nu mice (non tumor bearing) given a single 3 mg/kg IV dose of either 5T4 antibody alone, 5T4-mcM MAD ADC (conventional cys-conjugation) or various 5T4 cys-mutant mcMMAD ADCs.

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 [1]
Clearance (CL) 0.61 mL/h/kg
A study was conducted to determine the pharmacokinetic parameters of human anti-5T4 antibody comprising a wild type IgG1 Fe region and human cys mutant anti-5T4 antibody site specifically conjugated to a payload (ADC) in female nu/nu mice (non tumor bearing) given a single 3 mg/kg IV dose of either 5T4 antibody alone, 5T4-mcM MAD ADC (conventional cys-conjugation) or various 5T4 cys-mutant mcMMAD ADCs.

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 [1]
General Information of The Activity Data Related to This ADC
Revealed Based on the Cell Line Data
Click To Hide/Show 6 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Half Maximal inhibitory Concentration (lC57) 
> 75000
ng/ml
CVCL_0511
EBV-related Burkitt lymphoma
Half Maximal inhibitory Concentration (lC56) 
16000
ng/ml
CVCL_0511
EBV-related Burkitt lymphoma
Half Maximal inhibitory Concentration (lC56) 
20000
ng/ml
CVCL_0419
Breast adenocarcinoma
Half Maximal inhibitory Concentration (lC50) 
40
ng/ml
CVCL_0417
Amelanotic melanoma
Half Maximal inhibitory Concentration (lC50) 
120
ng/ml
CVCL_0417
Amelanotic melanoma
Half Maximal inhibitory Concentration (lC50) 
1400
ng/ml
CVCL_0419
Breast adenocarcinoma
Full List of Activity Data of This Antibody-drug Conjugate
Revealed Based on the Cell Line Data
Click To Hide/Show 6 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC57) > 75000 ng/ml Negative 5T4 expression (5T4-)
Method Description
The 5T4 Cys-mutated mcMMAD and vcMMAD ADCs were each able to inhibit the growth of the 5T4 expressing cell lines MDAMB435/57T4 (a high 514 expressor) and MDAMB-468 (a HER2 resistant cell line with moderate 5T4 expression).
In Vitro Model EBV-related Burkitt lymphoma Raji cells CVCL_0511
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC56) 16000 ng/ml Negative 5T4 expression (5T4-)
Method Description
The 5T4 Cys-mutated mcMMAD and vcMMAD ADCs were each able to inhibit the growth of the 5T4 expressing cell lines MDAMB435/57T4 (a high 514 expressor) and MDAMB-468 (a HER2 resistant cell line with moderate 5T4 expression).
In Vitro Model EBV-related Burkitt lymphoma Raji cells CVCL_0511
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC56) 20000 ng/ml Positive 5T4 expression (5T4+++/++)
Method Description
The 5T4 Cys-mutated mcMMAD and vcMMAD ADCs were each able to inhibit the growth of the 5T4 expressing cell lines MDAMB435/57T4 (a high 514 expressor) and MDAMB-468 (a HER2 resistant cell line with moderate 5T4 expression).
In Vitro Model Breast adenocarcinoma MDA-MB-468 cells CVCL_0419
Experiment 4 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50) 40 ng/ml Positive 5T4 expression (5T4+++/++)
Method Description
The 5T4 Cys-mutated mcMMAD and vcMMAD ADCs were each able to inhibit the growth of the 5T4 expressing cell lines MDAMB435/57T4 (a high 514 expressor) and MDAMB-468 (a HER2 resistant cell line with moderate 5T4 expression).
In Vitro Model Amelanotic melanoma MDA?MB?435 cells (5t4+) CVCL_0417
Experiment 5 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50) 120 ng/ml Positive 5T4 expression (5T4+++/++)
Method Description
The 5T4 Cys-mutated mcMMAD and vcMMAD ADCs were each able to inhibit the growth of the 5T4 expressing cell lines MDAMB435/57T4 (a high 514 expressor) and MDAMB-468 (a HER2 resistant cell line with moderate 5T4 expression).
In Vitro Model Amelanotic melanoma MDA?MB?435 cells (5t4+) CVCL_0417
Experiment 6 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50) 1400 ng/ml Positive 5T4 expression (5T4+++/++)
Method Description
The 5T4 Cys-mutated mcMMAD and vcMMAD ADCs were each able to inhibit the growth of the 5T4 expressing cell lines MDAMB435/57T4 (a high 514 expressor) and MDAMB-468 (a HER2 resistant cell line with moderate 5T4 expression).
In Vitro Model Breast adenocarcinoma MDA-MB-468 cells CVCL_0419
References
Ref 1 Engineered antibody constant regions for site-specific conjugation and methods and uses therefor