Antibody Information

General Information of This Antibody
Antibody ID
ANI0BKVFA
Antibody Name
Milatuzumab
Organization
Immunomedics, Inc.
Indication
Systemic lupus erythematosus; Acute lymphoblastic leukemia; B-cell chronic lymphocytic leukemia; Multiple myeloma
Synonyms
hLL1; IMMU-115
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Antibody Type
Monoclonal antibody (mAb)
Antibody Subtype
Humanized IgG1-kappa
Antigen Name
HLA class II histocompatibility antigen gamma chain (CD74)
  Antigen Info 
ChEMBI ID
CHEMBL1743040
DrugBank ID
DB12943
Click to Show/Hide the Sequence Information of This Antibody
Heavy Chain Sequence
QVQLQQSGSELKKPGASVKVSCKASGYTFTNYGVNWIKQAPGQGLQWMGWINPNTGEPTF
DDDFKGRFAFSLDTSVSTAYLQISSLKADDTAVYFCSRSRGKNEAWFAYWGQGTLVTVSS
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS
GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGG
PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN
STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE
MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW
QQGNVFSCSVMHEALHNHYTQKSLSLSPGK
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Heavy Chain Varible Domain
QVQLQQSGSELKKPGASVKVSCKASGYTFTNYGVNWIKQAPGQGLQWMGWINPNTGEPTF
DDDFKGRFAFSLDTSVSTAYLQISSLKADDTAVYFCSRSRGKNEAWFAYWGQGTLVTVSS
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Heavy Chain Constant Domain 1
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS
GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRV
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Heavy Chain Constant Domain 2
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK
PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
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Heavy Chain Constant Domain 3
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS
DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
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Heavy Chain Hinge Region
EPKSCDKTHTCPPCP
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Heavy Chain CDR 1
GYTFTNYG
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Heavy Chain CDR 2
INPNTGEP
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Heavy Chain CDR 3
SRSRGKNEAWFAY
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Light Chain Sequence
DIQLTQSPLSLPVTLGQPASISCRSSQSLVHRNGNTYLHWFQQRPGQSPRLLIYTVSNRF
SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYFCSQSSHVPPTFGAGTRLEIKRTVAAPSV
FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
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Light Chain Varible Domain
DIQLTQSPLSLPVTLGQPASISCRSSQSLVHRNGNTYLHWFQQRPGQSPRLLIYTVSNRF
SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYFCSQSSHVPPTFGAGTRLEIK
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Light Chain Constant Domain
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD
SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
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Light Chain CDR 1
QSLVHRNGNTY
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Light Chain CDR 2
TVS
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Light Chain CDR 3
SQSSHVPPT
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The Activity Data of This Antibody
Antibody Activity Information 1 [1]
Dissociation Constant (Kd)
0.50±0.02
nM
MC/CAR cells CVCL_1397 
Antigen Expression Positive CD74 expression (CD74+++/++)
Antibody Function In vitro cell binding experiments were done to determine the targeting effectiveness of IMMU-110 to CD74-positive MC/CAR cells.
Antibody Antigen Binding Assay Cell binding of IMMU-110 to MC/CAR cells was determined by an indirect cell surface binding ELISA.
Each Antibody-drug Conjugate Related to This Antibody
Full Information of The Activity Data of The ADC(s) Related to This Antibody
Milatuzumab doxorubicin [Phase 1/2 (discontinued)]
 ADC Info 
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)
0.8 uM
Positive CD74 expression (CD74+++/++)
Method Description
Briefly, cells were placed in 96-well plates (2 x105 per well) and subsequently incubated with serial dilutions of IMMU-110,naked hLL1,nonspecific negative control mAb-drug conjugate (hRS7-doxorubicin),or nonspecific mAb (hRS7) on ice for 1.5 hours. 4-hour IC50 values of IMMU-110,hRS7-doxorubicin,and free doxorubicin against the multiple myeloma cell line (MC/CAR) and other CD74-positive non-Hodgkin's lymphoma cell lines (Daudi and Raji).

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In Vitro Model EBV-related Burkitt lymphoma Raji cells CVCL_0511
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.9 uM
Positive CD74 expression (CD74+++/++)
Method Description
Briefly, cells were placed in 96-well plates (2 x105 per well) and subsequently incubated with serial dilutions of IMMU-110,naked hLL1,nonspecific negative control mAb-drug conjugate (hRS7-doxorubicin),or nonspecific mAb (hRS7) on ice for 1.5 hours. 4-hour IC50 values of IMMU-110,hRS7-doxorubicin,and free doxorubicin against the multiple myeloma cell line (MC/CAR) and other CD74-positive non-Hodgkin's lymphoma cell lines (Daudi and Raji).

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In Vitro Model Normal MC/CAR cells CVCL_1397
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.5 uM
Positive CD74 expression (CD74+++/++)
Method Description
Briefly, cells were placed in 96-well plates (2 x105 per well) and subsequently incubated with serial dilutions of IMMU-110,naked hLL1,nonspecific negative control mAb-drug conjugate (hRS7-doxorubicin),or nonspecific mAb (hRS7) on ice for 1.5 hours. 4-hour IC50 values of IMMU-110,hRS7-doxorubicin,and free doxorubicin against the multiple myeloma cell line (MC/CAR) and other CD74-positive non-Hodgkin's lymphoma cell lines (Daudi and Raji).

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In Vitro Model Burkitt lymphoma Daudi cells CVCL_0008
Identified from the Human Clinical Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Patients Enrolled
Eligible patients (≥18 years) must have recurrent B-cell NHL or CLL (≥1 prior therapy), measurable disease, and adequate organ/hematologic function, while excluding those with active HBV/HCV/HIV, heart failure, uncontrolled arrhythmias, recent cardiac events, autoimmune diseases, bulky tumors (>10cm), steroid dependence (>20mg/day prednisone), or pregnancy/lactation. Allogeneic transplant recipients ≥12 weeks post-procedure may enroll.

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Administration Dosage
hLL1-DOX is administered intravenously at one of 4 dose levels on days 1, 4, 8 and 11 of 21-day treatment cycles, with up to 8 cycles administered.
Related Clinical Trial
NCT Number NCT01585688  Clinical Status PHASE1|||PHASE2
Clinical Description
A Phase I/II Study of Immunotherapy With hLL1-DOX in Patients With Non-Hodgkin's Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL)
Primary Endpoint
The study assesses hLL1-DOX's safety profile using NCI CTCAE v4.0 for AE grading and evaluates efficacy through response rates (PR/CR) per dose level, with Kaplan-Meier analysis for progression-free survival (time to progression/death) and duration of response (time from response to relapse), monitoring patients every 3 months for up to 2 years post-treatment.

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Experiment 2 Reporting the Activity Date of This ADC [3]
Patients Enrolled
Eligibility requires relapsed/refractory MM (≥2 prior therapies including immunomodulators/PIs), measurable disease, Karnofsky ≥70%, and adequate organ function, while excluding transplant candidates, prior anthracycline exposure >300mg/m2, active HIV/HBV/HCV, autoimmune disorders, recent radiation/chemotherapy (14-28 days), or uncontrolled comorbidities. Pregnancy and inadequate contraception are exclusionary.

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Administration Dosage
hLL1-DOX will be administered intravenously (through a vein) on days 1, 4, 8 & 11 every 21 days for up to 8 treatment cycles. 4 different dose levels of hLL1-DOX will be studied for safety and tolerability.
Related Clinical Trial
NCT Number NCT01101594  Clinical Status PHASE1|||PHASE2
Clinical Description
A Phase I/II Study of hLL1-DOX (Milatuzumab-Doxorubicin Antibody-Drug Conjugate) in Patients With Multiple Myeloma
Primary Endpoint
Safety will be analyzed for all treated patients with intensive monitoring (pre-infusion, every 15min during infusion, plus 30/60/90/120min post-infusion), categorizing AEs by MedDRA v8.0 SOC/Preferred Term and NCI CTC v3 toxicity grades per dose cohort.
Other Endpoint
The efficacy population includes patients receiving ≥1 full dose with response data, evaluating IMWG response rates, response duration, and PFS by descriptive statistics across dose groups, assessed at 4/8/12 weeks then quarterly for 2 years.
Milatuzumab-RSL3-NH2 [Investigative]
 ADC Info 
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 [4]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
2.4 nM
High CD74 expression (CD74+++)
Method Description
The inhibitory activity of Milatuzumab-RSL3-NH2 against cancer cell growth was evaluated by MTT cytotoxicity assay.
In Vitro Model Diffuse large B-cell lymphoma Toledo cells CVCL_3611
References
Ref 1 Anti-CD74 antibody-doxorubicin conjugate, IMMU-110, in a human multiple myeloma xenograft and in monkeys. Clin Cancer Res. 2005 Jul 15;11(14):5257-64.
Ref 2 Phase I/II Study of hLL1-DOX in Relapsed NHL and CLL
Ref 3 A Study of hLL1-DOX (Milatuzumab-Doxorubicin Antibody-Drug Conjugate) in Patients With Multiple Myeloma
Ref 4 The first ADC bearing the ferroptosis inducer RSL3 as a payload with conservation of the fragile electrophilic warhead. Eur J Med Chem. 2022 Dec 15;244:114863.