Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0MFUNL
ADC Name
B-B4-DM1
Synonyms
CD138-targeted MAb-DM1 conjugate (Aventis); CD138-targeted MAb-DM1 conjugate (Immunogen); CD138-targeted MAb-DM1 conjugate (sanofi-aventis); B B4 DM1; B-B4 DM1
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Organization
ImmunoGen, Inc.; Sanofi
Drug Status
Investigative
Indication
In total 2 Indication(s)
B-cell lymphoma [ICD11:2A86]
Investigative
Multiple myeloma [ICD11:2A83]
Investigative
Drug-to-Antibody Ratio
3.5
Antibody Name
Cantuzumab
  Antibody Info 
Antigen Name
Syndecan-1 (SDC1)
  Antigen Info 
Payload Name
Mertansine DM1
  Payload Info 
Therapeutic Target
Microtubule (MT)
  Target Info 
Linker Name
Undisclosed
Conjugate Type
DM1 was converted to the disulfide-containing maytansinoid DM1, then conjugated to the monoclonal antibody huC242 directly.
General Information of The Activity Data Related to This ADC
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Standard Type Value Units Animal Model (No. of PDX)
Tumor Growth Inhibition value (TGI) 
≈ 87.9
%
Multiple myeloma PDX model (PDX: OPM2)
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Tumor Growth Inhibition value (TGI) 
≈ 27.3
%
Multiple myeloma cells
Multiple myeloma
Revealed Based on the Cell Line Data
Click To Hide/Show 1 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Half Maximal Inhibitory Concentration (IC50) 
25
nM
MM1.R cells
Plasma cell myeloma
Full List of Activity Data of This Antibody-drug Conjugate
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 87.90% Positive CD138 expression (CD138+++/++)
Method Description
The in vivo antitumor activity of B-B4-DM1 was evaluated in a CD138 positive OPM1 and OPM2 MM cells xenograft models. CB-17 SCID mice were inoculated subcutaneously in the interscapular area with 5x106 OPM1 (A-B) or OPM2 (C-D) MM cells. Animals were treated daily intravenously for 3 consecutive days with either vehicle alone (PBS; n = 5), unconjugated B-B4 (13.3 ug/kg; n = 5), B-B4DM1 (150 ug DM1/kg; n = 5), or control huC242-DM1 (150 ug DM1/kg; n = 5).

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In Vivo Model Multiple myeloma PDX model (PDX: OPM2)
In Vitro Model Multiple myeloma Multiple myeloma cells Homo sapiens
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 27.30% Positive CD138 expression (CD138+++/++)
Method Description
The in vivo antitumor activity of B-B4-DM1 was evaluated in a CD138 positive OPM1 and OPM2 MM cells xenograft models. CB-17 SCID mice were inoculated subcutaneously in the interscapular area with 5x106 OPM1 (A-B) or OPM2 (C-D) MM cells. Animals were treated daily intravenously for 3 consecutive days with either vehicle alone (PBS; n = 5), unconjugated B-B4 (13.3 ug/kg; n = 5), B-B4DM1 (150 ug DM1/kg; n = 5), or control huC242-DM1 (150 ug DM1/kg; n = 5).

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In Vivo Model CD138-expressing OPM1 MM cells xenograft model
In Vitro Model Multiple myeloma Multiple myeloma cells Homo sapiens
Revealed Based on the Cell Line Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 25.00 nM Positive CD138 expression (CD138+++/++)
Method Description
The inhibitory activity of B-B4-DM1 against cancer cell growth was compared with B-B4 and DM1 against cancer cell growth in vitro. The cells were treated with B-B4-DM1, B-B4 and DM1 for 96 hours.
In Vitro Model Plasma cell myeloma MM1.R cells CVCL_8794
References
Ref 1 Cytotoxic activity of the maytansinoid immunoconjugate B-B4-DM1 against CD138+ multiple myeloma cells. Blood. 2004 Dec 1;104(12):3688-96.

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