Delving into the Latest Updates on Milatuzumab with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Humanised anti-CD74, Milatuzumab (USAN)

+ [2]

Target

CD74

Mechanism

CD74 inhibitors(HLA-DR antigens-associated invariant chain inhibitors)

Therapeutic Areas

Immune System DiseasesSkin and Musculoskeletal Diseases

Active Indication

Systemic Lupus Erythematosus

Inactive Indication

Acute Graft Versus Host DiseaseAcute Lymphoblastic LeukemiaAcute Myeloid Leukemia+ [10]

Originator Organization

Immunomedics, Inc.

Active Organization

Immunomedics, Inc.

Inactive Organization

Gilead Sciences, Inc.

Drug Highest PhasePhase 2

First Approval Date-

RegulationOrphan Drug (US)

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Gene Sequence

Sequence Code 13007608L

Source: *****

Sequence Code 9976219H

Source: *****

The primary objectives are to evaluate the safety and tolerability of hLL1-DOX, and to determine the maximum tolerated dose (MTD) regimen (in terms of a dose and its associated dosing schedule). The secondary objectives are to obtain information on efficacy, pharmacodynamics, pharmacokinetics, and immunogenicity, and to determine the optimal dose for subsequent studies.

Start Date01 Aug 2012

Sponsor / Collaborator

Gilead Sciences, Inc.

NCT00989586 / CompletedPhase 1/2IIT

A Phase I/II Study of Veltuzumab (IMMU-106, hA20), a Humanized Anti-CD20 Monoclonal Antibody, Combined With Milatuzumab (IMMU-115, hLL1), a Humanized Anti-CD74 Monoclonal Antibody, in Relapsed and Refractory B-cell Non-Hodgkin's Lymphoma

A phase I dose escalation study of veltuzumab and milatuzumab in relapsed and refractory B-cell NHL. The phase I study will be followed by a pilot phase II study.

Start Date01 Sep 2009

Sponsor / Collaborator

Ohio State University Comprehensive Cancer Center

[+1]

100 Clinical Results associated with Milatuzumab

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100 Translational Medicine associated with Milatuzumab

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100 Patents (Medical) associated with Milatuzumab

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34

Literatures (Medical) associated with Milatuzumab

01 Dec 2022·European Journal of Medicinal Chemistry

The first ADC bearing the ferroptosis inducer RSL3 as a payload with conservation of the fragile electrophilic warhead

Article

Author: Conilh, Louise ; Boumendjel, Ahcène ; Falson, Pierre ; Dumontet, Charles ; Nguyen, Kim-Anh

The iron-dependent, non-apoptotic cell death, known as ferroptosis is an emerging strategy for the development of anticancer drugs. RSL3 was identified as an activator of ferroptosis through the inhibition of the glutathione peroxidase 4 (GPX4) which plays a crucial role in the cellular lipid oxidative stress. RSL3 is characterized by the presence of an electrophilic chloroacetyl moiety, namely warhead which covalently bonds to the catalytic and nucleophilic selenocysteine residue (Sec46) of GPX4. Like the major ferroptosis inducers, RSL3 suffers from lack of selectivity toward tumor cells. In this study, we report the first synthesis of an antibody-drug conjugate (ADC) containing RSL3 fragment and trastuzumab with the aim to deliver the agent selectively to tumors. The synthesis uses a judiciously chosen strategy to preserve the vital but fragile warhead. Full characterization of the ADC was accomplished, demonstrating the generation of a homogeneous DAR 8 conjugate. The robustness of the synthesis was successfully applied to another ADC associating the anti-CD74 mAb milatuzumab. The ADC induces ferroptotic cell death through reactive oxygen species accumulation and increases the activity of doxorubicin. The ADC associating trastuzumab and RSL3 may therefore offer potential applications in vectorized therapy alone or in combination with conventional chemotherapies.

01 Jul 2021·Annals of the Rheumatic DiseasesQ1 · MEDICINE

Experience with milatuzumab, an anti-CD74 antibody against immunomodulatory macrophage migration inhibitory factor (MIF) receptor, for systemic lupus erythematosus (SLE)

Q1 · MEDICINE

Letter

Author: Wegener, William A ; Wallace, Daniel J ; Goldenberg, David M ; Figueras, Florence

Milatuzumab (hLL1) is a humanised IgG1κ antibody that reacts with a cell surface epitope of human CD74, the human leukocyte antigen (HLA) class-II associated invariant chain present on antigen-presenting cells (APCs), including B cells and dendritic cells.1 Although initially studied for oncologic malignancies,2–5 dysregulation of APCs may also occur in non-malignant disorders, and several preclinical studies showed that milatuzumab modestly inhibited B cell proliferation, enhanced spontaneous migration, alterations of adhesion molecule expression and chemotaxis important for lymphocyte recruitment,6 and also reduced production of interferon-α in stimulated peripheral blood mononuclear cells isolated from healthy donors and patients with systemic lupus erythematosus (SLE) (unpublished results). Migration inhibitory factor (MIF) is a cytokine that activates a multicomponent receptor comprising the CD74 ligand-binding …

01 Jul 2018·British Journal of HaematologyQ2 · MEDICINE

A phase I‐II clinical trial of the anti‐CD74 monoclonal antibody milatuzumab in frail patients with refractory chronic lymphocytic leukaemia: A patient based approach

Q2 · MEDICINE

Article

Author: Berrebi, Alain ; Haran, Michal ; Shevetz, Olga ; Valinsky, Liora ; Shvidel, Lev ; Shtalrid, Mordechai ; Braester, Andrei ; Amram, Orna ; Shachar, Idit ; Mordich, Orly ; Greenberg, Shulamit ; Herishanu, Yair ; Marom, Ayelet ; Ruchlemer, Rosa ; Harpaz, Nurith ; Mirkin, Vita ; Shtreiter, Marina ; Binsky‐Ehrenreich, Inbal

100 Deals associated with Milatuzumab

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External Link

KEGG	Wiki	ATC	Drug Bank
D08944	Milatuzumab	-	DB12943

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Myeloid Leukemia	Phase 3	US	Gilead Sciences, Inc.	01 Dec 2013
Chronic Lymphocytic Leukemia	Phase 3	US	Gilead Sciences, Inc.	01 Aug 2008
Systemic Lupus Erythematosus	Phase 2	-	Immunomedics, Inc.	-
Multiple Myeloma	Phase 1	US	Immunomedics, Inc.	-
Lupus Erythematosus, Discoid	Preclinical	US	Immunomedics, Inc.	01 Jan 2007
Lupus Nephritis	Preclinical	US	Immunomedics, Inc.	01 Jan 2007
Lupus Vasculitis, Central Nervous System	Preclinical	US	Immunomedics, Inc.	01 Jan 2007
Plasmacytoma	Preclinical	US	Immunomedics, Inc.	01 Jan 2007
B-cell lymphoma refractory	Discovery	US	Gilead Sciences, Inc.	01 Sep 2009
Chronic lymphocytic leukaemia refractory	Discovery	IL	Gilead Sciences, Inc.	01 Apr 2009

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00989586 (Pubmed \| Int J Radiat Oncol Biol Phys) Manual	Phase 1/2	B-Cell Lymphoma	35	milatuzumab+veltuzumab	(xlvkyyviie) = hydprldhoj szgxlyatew (yrcgxwhsdz ) View more	Positive	01 Jun 2015
				Veltuzumab 200 mg/m(2) weekly + Milatuzumab 16 mg/kg weekly	-
NCT00421525 (Pubmed \| Int J Radiat Oncol Biol Phys)	Phase 1	Plasma cell myeloma refractory	25	Milatuzumab 1.5 mg/kg	kbuyxdlcsb(ywmriypxkx) = moderately decreased with treatment (median decrease, 34%) mgzsquvqui (agytdzpsqo ) View more	-	01 Nov 2013
				Milatuzumab 4.0 mg/kg