Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)

ADC ID	DRG0TDKHC
ADC Name	HER2-gsADC-48
Synonyms	HER2 gsADC 48 Click to Show/Hide
Drug Status	Investigative
Indication	In total 2 Indication(s) Breast cancer [ICD11:2C60-2C65] Investigative Gastric cancer [ICD11:2B72] Investigative
Drug-to-Antibody Ratio	2
	3D MOL	2D MOL
Antibody Name	Trastuzumab		Antibody Info
Antigen Name	Receptor tyrosine-protein kinase erbB-2 (ERBB2)		Antigen Info
Payload Name	Monomethyl auristatin E		Payload Info
Therapeutic Target	Microtubule (MT)		Target Info
Linker Name	2-Aminobenzamide oxime		Linker Info
Conjugate Type	LacNAc-based glycosite-specific conjudate through reduced inter-chain cysteines

General Information of The Activity Data Related to This ADC

Discovered Using Cell Line-derived Xenograft Model

Click To Hide/Show 2 Activity Data Related to This Level

Standard Type	Value	Units	Cell Line	Disease Model
Tumor Growth Inhibition value (TGI)	≈ 56.18	%	NCI-N87 cells	Gastric tubular adenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 98.5	%	NCI-N87 cells	Gastric tubular adenocarcinoma

Revealed Based on the Cell Line Data

Click To Hide/Show 3 Activity Data Related to This Level

Standard Type	Value	Units	Cell Line	Disease Model
Half Maximal Inhibitory Concentration (IC50)	0.08	nM	SK-BR-3 cells	Breast adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	0.09	nM	NCI-N87 cells	Gastric tubular adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	> 66	nM	MDA-MB-231 cells	Breast adenocarcinoma

Full List of Activity Data of This Antibody-drug Conjugate

Discovered Using Cell Line-derived Xenograft Model

Click To Hide/Show 2 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 56.18% (Day 28)	Positive HER2 expression (HER2+++/++)
Method Description	To further evaluate the gsADCs, we determined the in vivo tumor-inhibitory activity in an NCI-N87 nude mice xenograft model. The mice were randomly grouped into 10 groups (n = 5), including a PBS control group, when the tumors grew to 200 mm³. The experimental groups were 3.0 mg/kg gsADCs q3d.
In Vivo Model	NCI-N87 CDX model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 98.50% (Day 57)	Positive HER2 expression (HER2+++/++)
Method Description	To further evaluate the gsADCs, we determined the in vivo tumor-inhibitory activity in an NCI-N87 nude mice xenograft model. The mice were randomly grouped into 10 groups (n = 5), including a PBS control group, when the tumors grew to 200 mm³. The experimental groups were 3.0 mg/kg gsADCs q3d.
In Vivo Model	NCI-N87 CDX model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

Revealed Based on the Cell Line Data

Click To Hide/Show 3 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.08 nM	Positive HER2 expression (HER2+++/++)
Method Description	Cells were cultured in a 10% fetal bovine serum (FBS)-containing RPMI 1640 medium and were planted into 96-well plates with 6000 cells per well. The plates were incubated overnight at 37°C in a 5% CO₂ cell incubator.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.09 nM	Positive HER2 expression (HER2+++/++)
Method Description	Cells were cultured in a 10% fetal bovine serum (FBS)-containing RPMI 1640 medium and were planted into 96-well plates with 6000 cells per well. The plates were incubated overnight at 37°C in a 5% CO₂ cell incubator.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 3 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 66.00 nM	Negative HER2 expression (HER2 -)
Method Description	Cells were cultured in a 10% fetal bovine serum (FBS)-containing RPMI 1640 medium and were planted into 96-well plates with 6000 cells per well. The plates were incubated overnight at 37°C in a 5% CO₂ cell incubator.
In Vitro Model	Breast adenocarcinoma	MDA-MB-231 cells		CVCL_0062

References

Ref 1	Hiding Payload Inside the IgG Fc Cavity Significantly Enhances the Therapeutic Index of Antibody-Drug Conjugates. J Med Chem. 2023 Jan 12;66(1):1011-1026. doi: 10.1021/acs.jmedchem.2c01812. Epub 2022 Dec 30.