Antibody Information

General Information of This Antibody

Antibody ID	ANI0RYVVV
Antibody Name	Losatuxizumab
Organization	AbbVie, Inc.
Indication	Solid tumors
Synonyms	ABT-806; PR-1316749 Click to Show/Hide
Antibody Type	Monoclonal antibody (mAb)
Antibody Subtype	Chimeric IgG1-kappa
Antigen Name	Epidermal growth factor receptor (EGFR)	Antigen Info
Click to Show/Hide the Sequence Information of This Antibody
Heavy Chain Sequence	EVQLQESGPGLVKPSQTLSLTCTVSGYSISRDFAWNWIRQPPGKGLEWMGYISYNGNTRY QPSLKSRITISRDTSKNQFFLKLNSVTAADTATYYCVTASRGFPYWGQGTLVTVSSASTK GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVF LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGK Click to Show/Hide
Heavy Chain Varible Domain	EVQLQESGPGLVKPSQTLSLTCTVSGYSISRDFAWNWIRQPPGKGLEWMGYISYNGNTRY QPSLKSRITISRDTSKNQFFLKLNSVTAADTATYYCVTASRGFPYWGQGTLVTVSS Click to Show/Hide
Heavy Chain Constant Domain 1	ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKV Click to Show/Hide
Heavy Chain Constant Domain 2	APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK Click to Show/Hide
Heavy Chain Constant Domain 3	GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK Click to Show/Hide
Heavy Chain Hinge Region	EPKSCDKTHTCPPCP Click to Show/Hide
Heavy Chain CDR 1	GYSISRDFA Click to Show/Hide
Heavy Chain CDR 2	ISYNGNT Click to Show/Hide
Heavy Chain CDR 3	VTASRGFPY Click to Show/Hide
Light Chain Sequence	DIQMTQSPSSMSVSVGDRVTITCHSSQDINSNIGWLQQKPGKSFKGLIYHGTNLDDGVPS RFSGSGSGTDYTLTISSLQPEDFATYYCVQYAQFPWTFGGGTKLEIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC Click to Show/Hide
Light Chain Varible Domain	DIQMTQSPSSMSVSVGDRVTITCHSSQDINSNIGWLQQKPGKSFKGLIYHGTNLDDGVPS RFSGSGSGTDYTLTISSLQPEDFATYYCVQYAQFPWTFGGGTKLEIK Click to Show/Hide
Light Chain Constant Domain	RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC Click to Show/Hide
Light Chain CDR 1	QDINSN Click to Show/Hide
Light Chain CDR 2	HGT Click to Show/Hide
Light Chain CDR 3	VQYAQFPWT Click to Show/Hide

Each Antibody-drug Conjugate Related to This Antibody

Full Information of The Activity Data of The ADC(s) Related to This Antibody

Losatuxizumab vedotin [Phase 1]

ADC Info

Identified from the Human Clinical Data

Click To Hide/Show 1 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC				[1]
Patients Enrolled	Patients with advanced solid tumor types typically associated with elevated levels of EGFR expression (e.g., head and neck squamous cell carcinoma [HNC], non-small cell lung cancer [NSCLC], triple-negative breast cancer, colorectal carcinoma, and GBM.
Administration Dosage	A standard 3+3 design; intravenous (IV) infusion to groups of 3 to 6 patients. An every-3-week dosing cycle (0.30, 0.45, 0.67, 1.00, 1.50, 2.00, or 2.25 mg/kg losatuxizumab vedotin every 3 weeks [Q3W]) or alternative dosing schedules were evaluated (2.00 or 3.00 mg/kg losatuxizumab vedotin for 2 weeks on, 1 week off, or 4.50 or 6.00 mg/kg losatuxizumab vedotin weekly [over 3 weeks total]). Click to Show/Hide
*Related Clinical Trial*
NCT Number	NCT02365662	Clinical Status	Phase 1
Clinical Description	A phase 1 study of ABBV-221 in subjects with advanced solid tumor types likely to exhibit elevated levels of epidermal growth factor receptor.
Primary Endpoint	The maximum tolerated dose (MTD) was not achieved.
Other Endpoint	Stable disease (SD) for at least 2 cycles was observed in 19 patients (42.20%).

Discovered Using Patient-derived Xenograft Model

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

Experiment 1 Reporting the Activity Date of This ADC				[2]
Efficacy Data	Tumor Growth Inhibition value (TGI)	94.90% (Day 49)	High HER2 expression (HER2+++)
Method Description	In vivo therapy studies were conducted in mesothelioma xenograft and patient-derived xenograft (PDX) tumor model.ABT-414 treatment 3 mg/kg q4 days.
In Vivo Model	Malignant Mesothelioma PDX model (PDX: MSTO-211H)
Experiment 2 Reporting the Activity Date of This ADC				[2]
Efficacy Data	Tumor Growth Inhibition value (TGI)	98.30% (Day 49)	High HER2 expression (HER2+++)
Method Description	In vivo therapy studies were conducted in mesothelioma xenograft and patient-derived xenograft (PDX) tumor model.ABBV-221 treatment 3 mg/kg q4 days.
In Vivo Model	Malignant Mesothelioma PDX model (PDX: MSTO-211H)

Discovered Using Cell Line-derived Xenograft Model

Click To Hide/Show 4 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 0.23% (Day 120)	Low EGFR expression (EGFR+)
Method Description	To generate xenografts, a suspension of viable tumors cells mixed with an equal amount of Matrigel was injected subcutaneously into the flank of 6- to 8-week old mice. The injection volume was 0.2 mL composed of a 1:1 mixture of S-MEM and Matrigel. Tumors were size matched at approximately 200-250 mm³. Treatments ABBV-221 at 6 mg/kg every 4th day by intraperitoneal injection. Click to Show/Hide
In Vivo Model	NCI-H292 lung xenograft tumor model
In Vitro Model	Lung mucoepidermoid carcinoma	NCI-H292 cells		CVCL_0455
Experiment 2 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 5.45% (Day 95)	Low EGFR expression (EGFR+)
Method Description	To generate xenografts, a suspension of viable tumors cells mixed with an equal amount of Matrigel was injected subcutaneously into the flank of 6- to 8-week old mice. The injection volume was 0.2 mL composed of a 1:1 mixture of S-MEM and Matrigel. Tumors were size matched at approximately 200-250 mm³. Treatments ABBV-221 at 3 mg/kg every 4th day by intraperitoneal injection. Click to Show/Hide
In Vivo Model	NCI-H441 lung xenograft tumor model
In Vitro Model	Lung papillary adenocarcinoma	NCI-H441 cells		CVCL_1561
Experiment 3 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 66.60% (Day 113)	High EGFR expression (EGFR+++)
Method Description	To generate xenografts, a suspension of viable tumors cells mixed with an equal amount of Matrigel was injected subcutaneously into the flank of 6- to 8-week old mice. The injection volume was 0.2 mL composed of a 1:1 mixture of S-MEM and Matrigel. Tumors were size matched at approximately 200-250 mm³. Treatments ABBV-221 at 4 mg/kg every 4th day by intraperitoneal injection. Click to Show/Hide
In Vivo Model	EBC1 lung xenograft tumor model
In Vitro Model	Lung squamous cell carcinoma	EBC-1 cells		CVCL_2891
Experiment 4 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 100.00% (Day 113)	High EGFR expression (EGFR+++)
Method Description	To generate xenografts, a suspension of viable tumors cells mixed with an equal amount of Matrigel was injected subcutaneously into the flank of 6- to 8-week old mice. The injection volume was 0.2 mL composed of a 1:1 mixture of S-MEM and Matrigel. Tumors were size matched at approximately 200-250 mm³. Treatments ABBV-221 at 1 mg/kg every 4th day by intraperitoneal injection. Click to Show/Hide
In Vivo Model	NCI-H1703 lung xenograft tumor model
In Vitro Model	Lung squamous cell carcinoma	NCI-H1703 cells		CVCL_1490

Revealed Based on the Cell Line Data

Click To Hide/Show 11 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 89.80% (Day 40)	Positive EGFR expression (EGFR+++/++)
Method Description	To establish xenografts, 2 x 10⁶ MSTO-211H cells mixed with 75-uL Matrigel were injected subcutaneously in the right flank of 5 to 6-week-old female BALB/c nu/nu miceFor the MSTO-211H study, mice received either ABT-414, ABBV-221 or ADC control (3 mg/kg) every 4 days.
In Vivo Model	MSTO-211H CDX model
In Vitro Model	Pleural biphasic mesothelioma	MSTO-211H cells		CVCL_1430
Experiment 2 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.20 nM	Positive EGFR vIII expression (EGFR vIII+++/++)
Method Description	Cells were plated at 1,000 to 3,000 cells/well in complete growth medium containing 10% FBS in 96-well plates. The following day medium was removed and replaced with fresh media containing titrations of antibodies or ADCs, and cells were incubated for 72 hours at 37°C in a humidified CO₂ incubator. Cell viability was then assessed using an ATPlite luminescence assay.Cell viability was determined following incubation with ABBV-221 for 72 hours. Click to Show/Hide
In Vitro Model	Glioblastoma	U87MGde2-7 cells (EGFRvIII overexpression)		CVCL_0022
Experiment 3 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	1.00 nM	High EGFR expression (EGFR+++)
Method Description	Cells were plated at 1,000 to 3,000 cells/well in complete growth medium containing 10% FBS in 96-well plates. The following day medium was removed and replaced with fresh media containing titrations of antibodies or ADCs, and cells were incubated for 72 hours at 37°C in a humidified CO₂ incubator. Cell viability was then assessed using an ATPlite luminescence assay.Cell viability was determined following incubation with ABBV-221 for 72 hours. Click to Show/Hide
In Vitro Model	Skin squamous cell carcinoma	A431 cells		CVCL_0037
Experiment 4 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	4.00 nM	High EGFR expression (EGFR+++)
Method Description	Cells were plated at 1,000 to 3,000 cells/well in complete growth medium containing 10% FBS in 96-well plates. The following day medium was removed and replaced with fresh media containing titrations of antibodies or ADCs, and cells were incubated for 72 hours at 37°C in a humidified CO₂ incubator. Cell viability was then assessed using an ATPlite luminescence assay.Cell viability was determined following incubation with ABBV-221 for 72 hours. Click to Show/Hide
In Vitro Model	Lung squamous cell carcinoma	NCI-H1703 cells		CVCL_1490
Experiment 5 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	8.00 nM	High EGFR expression (EGFR+++)
Method Description	Cells were plated at 1,000 to 3,000 cells/well in complete growth medium containing 10% FBS in 96-well plates. The following day medium was removed and replaced with fresh media containing titrations of antibodies or ADCs, and cells were incubated for 72 hours at 37°C in a humidified CO₂ incubator. Cell viability was then assessed using an ATPlite luminescence assay.Cell viability was determined following incubation with ABBV-221 for 72 hours. Click to Show/Hide
In Vitro Model	Lung mucoepidermoid carcinoma	NCI-H292 cells		CVCL_0455
Experiment 6 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	8.00 nM	High EGFR expression (EGFR+++)
Method Description	Cells were plated at 1,000 to 3,000 cells/well in complete growth medium containing 10% FBS in 96-well plates. The following day medium was removed and replaced with fresh media containing titrations of antibodies or ADCs, and cells were incubated for 72 hours at 37°C in a humidified CO₂ incubator. Cell viability was then assessed using an ATPlite luminescence assay.Cell viability was determined following incubation with ABBV-221 for 72 hours. Click to Show/Hide
In Vitro Model	Colon adenocarcinoma	LoVo cells		CVCL_0399
Experiment 7 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	11.00 nM	High EGFR expression (EGFR+++)
Method Description	Cells were plated at 1,000 to 3,000 cells/well in complete growth medium containing 10% FBS in 96-well plates. The following day medium was removed and replaced with fresh media containing titrations of antibodies or ADCs, and cells were incubated for 72 hours at 37°C in a humidified CO₂ incubator. Cell viability was then assessed using an ATPlite luminescence assay.Cell viability was determined following incubation with ABBV-221 for 72 hours. Click to Show/Hide
In Vitro Model	Lung adenocarcinoma	HCC827ER cells		CVCL_V408
Experiment 8 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	69.00 nM	Moderate EGFR expression (EGFR++)
Method Description	Cells were plated at 1,000 to 3,000 cells/well in complete growth medium containing 10% FBS in 96-well plates. The following day medium was removed and replaced with fresh media containing titrations of antibodies or ADCs, and cells were incubated for 72 hours at 37°C in a humidified CO₂ incubator. Cell viability was then assessed using an ATPlite luminescence assay.Cell viability was determined following incubation with ABBV-221 for 72 hours. Click to Show/Hide
In Vitro Model	Lung squamous cell carcinoma	EBC-1 cells		CVCL_2891
Experiment 9 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	80.00 nM	Moderate EGFR expression (EGFR++)
Method Description	Cells were plated at 1,000 to 3,000 cells/well in complete growth medium containing 10% FBS in 96-well plates. The following day medium was removed and replaced with fresh media containing titrations of antibodies or ADCs, and cells were incubated for 72 hours at 37°C in a humidified CO₂ incubator. Cell viability was then assessed using an ATPlite luminescence assay.Cell viability was determined following incubation with ABBV-221 for 72 hours. Click to Show/Hide
In Vitro Model	Lung papillary adenocarcinoma	NCI-H441 cells		CVCL_1561
Experiment 10 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 1000.00 nM	Low EGFR expression (EGFR+)
Method Description	Cells were plated at 1,000 to 3,000 cells/well in complete growth medium containing 10% FBS in 96-well plates. The following day medium was removed and replaced with fresh media containing titrations of antibodies or ADCs, and cells were incubated for 72 hours at 37°C in a humidified CO₂ incubator. Cell viability was then assessed using an ATPlite luminescence assay.Cell viability was determined following incubation with ABBV-221 for 72 hours. Click to Show/Hide
In Vitro Model	Colon adenocarcinoma	HCT 15 cells		CVCL_0292
Experiment 11 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 1000.00 nM	Low EGFR expression (EGFR+)
Method Description	Cells were plated at 1,000 to 3,000 cells/well in complete growth medium containing 10% FBS in 96-well plates. The following day medium was removed and replaced with fresh media containing titrations of antibodies or ADCs, and cells were incubated for 72 hours at 37°C in a humidified CO₂ incubator. Cell viability was then assessed using an ATPlite luminescence assay.Cell viability was determined following incubation with ABBV-221 for 72 hours. Click to Show/Hide
In Vitro Model	Colon adenocarcinoma	SW620 cells		CVCL_0547

References

Ref 1	A phase 1 study evaluating safety and pharmacokinetics of losatuxizumab vedotin (ABBV-221), an anti-EGFR antibody-drug conjugate carrying monomethyl auristatin E, in patients with solid tumors likely to overexpress EGFR. Invest New Drugs. 2020 Oct;38(5):1483-1494.
Ref 2	Targeting and Efficacy of Novel mAb806-Antibody-Drug Conjugates in Malignant Mesothelioma. Pharmaceuticals (Basel). 2020 Oct 2;13(10):289.
Ref 3	Characterization of ABBV-221, a Tumor-Selective EGFR-Targeting Antibody Drug Conjugate. Mol Cancer Ther. 2018 Apr;17(4):795-805.
Ref 4	Targeting and Efficacy of Novel mAb806-Antibody-Drug Conjugates in Malignant Mesothelioma. Pharmaceuticals (Basel). 2020 Oct 2;13(10):289. doi: 10.3390/ph13100289.

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Correspondence

Prof. Feng ZHU (zhufeng@zju.edu.cn)

Prof. Xiaowu DONG (dongxw@zju.edu.cn)

Prof. Luo FANG (fangluo@zjcc.org.cn)