Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0YMGHL
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| ADC Name |
LA-057-MMAE
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| Synonyms |
LA-057-MMAE
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| Organization |
Fudan University.; Shanghai Junshi Biosciences Co., Ltd.
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| Drug Status |
Investigative
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| Drug-to-Antibody Ratio |
3.71
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| Structure |
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| Antibody Name |
LA-057
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Antibody Info | ||||
| Antigen Name |
Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1)
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Antigen Info | ||||
| Payload Name |
Monomethyl auristatin E
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Payload Info | ||||
| Therapeutic Target |
Microtubule (MT)
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Target Info | ||||
| Linker Name |
Mc-Val-Cit-PABC
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Linker Info | ||||
| Conjugate Type |
Random conjugation through reduced inter-chain cysteines.
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| Combination Type |
Vedotin
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ADC-specific functional property(2027 Update)
Binding Affinity
| Dissocation Constant (Kd) | Binding Target | Description | Reference |
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| 3.9 nM |
hLAIR1
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The affinity values for LA-057-MMAE binding to hLAIR1 and rhesus LAIR1 were 3.90 nM and 10.1 nM, respectively.
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[1]
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| 10.1 nM |
LAIR1
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The affinity values for LA-057-MMAE binding to hLAIR1 and rhesus LAIR1 were 3.90 nM and 10.1 nM, respectively.
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[1]
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General Information of The ADMET Data Related to This ADC(2027 Update)
Absorption
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 235 | day*ug/mL |
Pharmacokinetic study of LA-057-MMAE in female CB-17 SCID mice (3 mg/kg, intravenous, single dose).
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 250 | day*ug/mL |
Pharmacokinetic study of LA-057-MMAE in female CB-17 SCID mice (3 mg/kg, intravenous, single dose).
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[1] |
Distribution
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Volume of Distribution (Vd) | 103 | mL/kg |
Pharmacokinetic study of LA-057-MMAE in female CB-17 SCID mice (3 mg/kg, intravenous, single dose).
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 235 | day*ug/mL |
Pharmacokinetic study of LA-057-MMAE in female CB-17 SCID mice (3 mg/kg, intravenous, single dose).
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 250 | day*ug/mL |
Pharmacokinetic study of LA-057-MMAE in female CB-17 SCID mice (3 mg/kg, intravenous, single dose).
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[1] |
Metabolism
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 235 | day*ug/mL |
Pharmacokinetic study of LA-057-MMAE in female CB-17 SCID mice (3 mg/kg, intravenous, single dose).
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 250 | day*ug/mL |
Pharmacokinetic study of LA-057-MMAE in female CB-17 SCID mice (3 mg/kg, intravenous, single dose).
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[1] |
Excretion
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Clearance (CL) | 12 | mL/day/kg |
Pharmacokinetic study of LA-057-MMAE in female CB-17 SCID mice (3 mg/kg, intravenous, single dose).
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[1] |
| Elimination Half-Life (t1/2) | 7.85 | day |
Pharmacokinetic study of LA-057-MMAE in female CB-17 SCID mice (3 mg/kg, intravenous, single dose).
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 235 | day*ug/mL |
Pharmacokinetic study of LA-057-MMAE in female CB-17 SCID mice (3 mg/kg, intravenous, single dose).
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 250 | day*ug/mL |
Pharmacokinetic study of LA-057-MMAE in female CB-17 SCID mice (3 mg/kg, intravenous, single dose).
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[1] |
General Information of The Activity Data Related to This ADC
Discovered Using Cell Line-derived Xenograft Model
Revealed Based on the Cell Line Data
Full List of Activity Data of This Antibody-drug Conjugate
Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) |
20%
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| Method Description |
1 mg/kg: Six-week-old B-NDG female mice (Biocytogen, China) were injected subcutaneously with 5 × 106 MV4-11 cells. Tumor growth was monitored, and mice were assigned to four treatment groups when tumor volumes reached approximately 100 mm3. Each group received two intravenous tail vein injections of one of the following treatments: vehicle or LA-057-MMAE (1, 3, and 6 mg/kg) on day 0 and 7. Tumor volume (V) = (LxW2)/2, where L is the longest dimension of the tumor and W is the corresponding tumor width. Mice were monitored for survival until they either succumbed to the disease or were euthanized when tumor volumes exceeded 1500 mm3.
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| In Vivo Model | MV-4-11 xenograft model | ||||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) |
86%
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| Method Description |
3 mg/kg: Six-week-old B-NDG female mice (Biocytogen, China) were injected subcutaneously with 5 × 106 MV4-11 cells. Tumor growth was monitored, and mice were assigned to four treatment groups when tumor volumes reached approximately 100 mm3. Each group received two intravenous tail vein injections of one of the following treatments: vehicle or LA-057-MMAE (1, 3, and 6 mg/kg) on day 0 and 7. Tumor volume (V) = (LxW2)/2, where L is the longest dimension of the tumor and W is the corresponding tumor width. Mice were monitored for survival until they either succumbed to the disease or were euthanized when tumor volumes exceeded 1500 mm3.
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| In Vivo Model | MV-4-11 xenograft model | ||||
| Experiment 3 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) |
114%
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| Method Description |
6 mg/kg: Six-week-old B-NDG female mice (Biocytogen, China) were injected subcutaneously with 5 × 106 MV4-11 cells. Tumor growth was monitored, and mice were assigned to four treatment groups when tumor volumes reached approximately 100 mm3. Each group received two intravenous tail vein injections of one of the following treatments: vehicle or LA-057-MMAE (1, 3, and 6 mg/kg) on day 0 and 7. Tumor volume (V) = (LxW2)/2, where L is the longest dimension of the tumor and W is the corresponding tumor width. Mice were monitored for survival until they either succumbed to the disease or were euthanized when tumor volumes exceeded 1500 mm3.
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| In Vivo Model | MV-4-11 xenograft model | ||||
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) | 0.02 nM | Positive LAIR1 expression (LAIR1+++/++) | ||
| Method Description |
LA-057-MMAE or isotype control-MMAE was serially diluted in cell culture media and added to AML cells (U937, MV-4-11, and HL60) at a density of 1 × 104 cells per well. The cells were incubated for different durations: U937 cells for 2 days, HL-60 cells for 6 days, and MV4-11 cells for 3 days. For AML patient PBMCs, 3000 cells per well were incubated with serially diluted ADC in StemSpan Leukemic Cell Culture kit (STEMCELL Technologies, USA) for 7 days. Cell viability was measured (Promega) and calculated the growth inhibition of each well by a percentage of cell viability relative to blank wells. The assays were conducted following the guidelines established by Junx Bio for the use of PBMCs from AML patients.
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| In Vitro Model | Acute monoblastic/monocytic leukemia, Adult acute monocytic leukemia | U937 cells | CVCL_0007 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) | 0.09 nM | Positive LAIR1 expression (LAIR1+++/++) | ||
| Method Description |
LA-057-MMAE or isotype control-MMAE was serially diluted in cell culture media and added to AML cells (U937, MV-4-11, and HL60) at a density of 1 × 104 cells per well. The cells were incubated for different durations: U937 cells for 2 days, HL-60 cells for 6 days, and MV4-11 cells for 3 days. For AML patient PBMCs, 3000 cells per well were incubated with serially diluted ADC in StemSpan Leukemic Cell Culture kit (STEMCELL Technologies, USA) for 7 days. Cell viability was measured (Promega) and calculated the growth inhibition of each well by a percentage of cell viability relative to blank wells. The assays were conducted following the guidelines established by Junx Bio for the use of PBMCs from AML patients.
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| In Vitro Model | Acute myeloblastic leukemia with maturation, Adult acute myeloid leukemia with maturation | HL60 cells | CVCL_0002 | ||
| Experiment 3 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) | 0.22 nM | Positive LAIR1 expression (LAIR1+++/++) | ||
| Method Description |
LA-057-MMAE or isotype control-MMAE was serially diluted in cell culture media and added to AML cells (U937, MV-4-11, and HL60) at a density of 1 × 104 cells per well. The cells were incubated for different durations: U937 cells for 2 days, HL-60 cells for 6 days, and MV4-11 cells for 3 days. For AML patient PBMCs, 3000 cells per well were incubated with serially diluted ADC in StemSpan Leukemic Cell Culture kit (STEMCELL Technologies, USA) for 7 days. Cell viability was measured (Promega) and calculated the growth inhibition of each well by a percentage of cell viability relative to blank wells. The assays were conducted following the guidelines established by Junx Bio for the use of PBMCs from AML patients.
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| In Vitro Model | Childhood acute monocytic leukemia | MV4-11 cells | CVCL_0064 | ||
References