General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0UCXTV
ADC Name
CAC10-DT
Synonyms
CAC10 DT
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Drug Status
Investigative
Indication
In total 2 Indication(s)
Anaplastic large cell lymphoma [ICD11:2A90]
Investigative
Hodgkin lymphoma [ICD11:2B30]
Investigative
Drug-to-Antibody Ratio
8
Antibody Name
Brentuximab
 Antibody Info 
Antigen Name
Tumor necrosis factor receptor superfamily member 8 (TNFRSF8)
 Antigen Info 
Payload Name
DX-8951 derivative (DXd)
 Payload Info 
Therapeutic Target
DNA topoisomerase 1 (TOP1)
 Target Info 
Linker Name
Mc-Gly-Gly-Phe-Gly
 Linker Info 
Conjugate Type
Random conjugation through reduced inter-chain cysteines.
Combination Type
Deruxtecan
General Information of The Activity Data Related to This ADC
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 9 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Tumor Growth Inhibition value (TGI) 
≈ 0
%
L-428 cells
Hodgkin lymphoma
Tumor Growth Inhibition value (TGI) 
≈ 0
%
L-428 cells
Hodgkin lymphoma
Tumor Growth Inhibition value (TGI) 
≈ 72
%
Karpas-299 cells/Karpas BVR cells
ALK-positive anaplastic large cell lymphoma
Tumor Growth Inhibition value (TGI) 
≈ 90
%
Karpas-299 cells/Karpas BVR cells
ALK-positive anaplastic large cell lymphoma
Half Maximal Inhibitory Concentration (IC50) 
7
ng/mL
ALCL cells
Precursor T-cell acute lymphoblastic leukemia
Half Maximal Inhibitory Concentration (IC50) 
16
ng/mL
DEL/BVR cells
Anaplastic large cell lymphoma
Half Maximal Inhibitory Concentration (IC50) 
26
ng/mL
L540cy cells
Hodgkin's disease
Half Maximal Inhibitory Concentration (IC50) 
> 1000
ng/mL
Karpas-299 cells
ALK-positive anaplastic large cell lymphoma
Half Maximal Inhibitory Concentration (IC50) 
> 1000
ng/mL
L-428 cells
Hodgkin lymphoma
Full List of Activity Data of This Antibody-drug Conjugate
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 9 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 0.00% (Day 51) Low CD30 expression (CD30+)
Method Description
Tumor cells, as suspensions, were implanted subcutaneously in SCID or nude mice. Upon tumor engraftment, mice were randomized to study groups (5 mice per group) when the average tumor volume reached about 100 mm3. The ADC or vehicle controls were dosed once via intraperitoneal injection. The dose of cAC10-DT=1 mg/kg.
In Vivo Model HD CDX model
In Vitro Model Hodgkin lymphoma L-428 cells CVCL_1361
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 0.00% (Day 51) Low CD30 expression (CD30+)
Method Description
Tumor cells, as suspensions, were implanted subcutaneously in SCID or nude mice. Upon tumor engraftment, mice were randomized to study groups (5 mice per group) when the average tumor volume reached about 100 mm3. The ADC or vehicle controls were dosed once via intraperitoneal injection. The dose of cAC10-DT=3 mg/kg.
In Vivo Model HD CDX model
In Vitro Model Hodgkin lymphoma L-428 cells CVCL_1361
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 72.00% (Day 11) Positive CD30 expression (CD30+++/++)
Method Description
Tumor cells, as suspensions, were implanted subcutaneously in SCID or nude mice. Upon tumor engraftment, mice were randomized to study groups (5 mice per group) when the average tumor volume reached about 100 mm3. The ADC or vehicle controls were dosed once via intraperitoneal injection. The dose of cAC10-DT=3 mg/kg.
In Vivo Model ALCL CDX model
In Vitro Model ALK-positive anaplastic large cell lymphoma Karpas-299 cells/Karpas BVR cells CVCL_1324
Experiment 4 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 90.00% (Day 11) Positive CD30 expression (CD30+++/++)
Method Description
Tumor cells, as suspensions, were implanted subcutaneously in SCID or nude mice. Upon tumor engraftment, mice were randomized to study groups (5 mice per group) when the average tumor volume reached about 100 mm3. The ADC or vehicle controls were dosed once via intraperitoneal injection. The dose of cAC10-DT=10 mg/kg.
In Vivo Model ALCL CDX model
In Vitro Model ALK-positive anaplastic large cell lymphoma Karpas-299 cells/Karpas BVR cells CVCL_1324
Experiment 5 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 7.00 ng/mL High CD30 expression (CD30+++; 285,000 CD30 molecules/cell)
Method Description
Serial dilutions of ADCs in cell culture media were prepared at 4x working concentrations, and 50 uL of each dilution was added to the 96-well plates. Following addition of test articles, cells were incubated for 4 days at 37°C, after which growth inhibition was assessed by the addition of CellTiter-Glo and luminescence was measured on a plate reader.

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In Vitro Model Precursor T-cell acute lymphoblastic leukemia ALCL cells CVCL_A036
Experiment 6 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 16.00 ng/mL High CD30 expression (CD30+++; 180,000 CD30 molecules/cell)
Method Description
Serial dilutions of ADCs in cell culture media were prepared at 4x working concentrations, and 50 uL of each dilution was added to the 96-well plates. Following addition of test articles, cells were incubated for 4 days at 37°C, after which growth inhibition was assessed by the addition of CellTiter-Glo and luminescence was measured on a plate reader.

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In Vitro Model Anaplastic large cell lymphoma DEL/BVR cells CVCL_1170
Experiment 7 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 26.00 ng/mL High CD30 expression (CD30+++; 400,000 CD30 molecules/cell)
Method Description
Serial dilutions of ADCs in cell culture media were prepared at 4x working concentrations, and 50 uL of each dilution was added to the 96-well plates. Following addition of test articles, cells were incubated for 4 days at 37°C, after which growth inhibition was assessed by the addition of CellTiter-Glo and luminescence was measured on a plate reader.

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In Vitro Model Hodgkin's disease L540cy cells Homo sapiens
Experiment 8 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 1000.00 ng/mL High CD30 expression (CD30+++; 320,000 CD30 molecules/cell)
Method Description
Serial dilutions of ADCs in cell culture media were prepared at 4x working concentrations, and 50 uL of each dilution was added to the 96-well plates. Following addition of test articles, cells were incubated for 4 days at 37°C, after which growth inhibition was assessed by the addition of CellTiter-Glo and luminescence was measured on a plate reader.

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In Vitro Model ALK-positive anaplastic large cell lymphoma Karpas-299 cells CVCL_1324
Experiment 9 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 1000.00 ng/mL Low CD30 expression (CD30+; 70,000 CD30 molecules/cell)
Method Description
Serial dilutions of ADCs in cell culture media were prepared at 4x working concentrations, and 50 uL of each dilution was added to the 96-well plates. Following addition of test articles, cells were incubated for 4 days at 37°C, after which growth inhibition was assessed by the addition of CellTiter-Glo and luminescence was measured on a plate reader.

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In Vitro Model Hodgkin lymphoma L-428 cells CVCL_1361
References
Ref 1 Development of Novel Antibody-Camptothecin Conjugates. Mol Cancer Ther. 2021 Feb;20(2):329-339.

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