Milatuzumab

Milatuzumab
Monoclonal antibody
Type	Whole antibody
Source	Humanized (from mouse)
Target	CD74
Clinical data
ATC code	none
Identifiers
CAS Number	899796-83-9^N
ChemSpider	none
UNII	2OP4E0GC6V
KEGG	D08944^Y
Chemical and physical data
Formula	C₆₅₁₈H₁₀₀₆₆N₁₇₅₈O₂₀₂₀S₄₀
Molar mass	146658.91 g·mol⁻¹
^NY (what is this?) (verify)

Milatuzumab (or hLL1) is an anti-CD74^[1] humanized monoclonal antibody for the treatment of multiple myeloma non-Hodgkin's lymphoma and chronic lymphocytic leukemia.^[2]^[3]

The drug is the first anti-CD74 antibody that has entered into human testing and is currently being studied for the treatment of multiple myeloma. Milatuzumab has received orphan drug designation from the Food and Drug Administration in the United States for the treatment of multiple myeloma and chronic lymphocytic leukemia.

Milatuzumab was developed by Immunomedics, Inc, (Morris Plains NJ USA).

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CD74

CD74 is present on a variety of hematological tumors and even on some solid cancers. It is present in limited amounts in normal tissues but widely found in leukemias, lymphomas and the vast majority of multiple myeloma cases.^{[citation needed]} CD74 is involved in a cell-to-cell communication pathway that is critical for survival.^{[citation needed]} When CD74 is blocked by milatuzumab, it can lead to cell death.

CD74 is an attractive target for a drug conjugate because of its rapid internalizing property.^{[citation needed]}

In preclinical studies with human lymphomas and myelomas, both naked Milatuzumab and the Milatuzumab conjugated with doxorubicin,^[4] an antibody-drug conjugate or ADC, have demonstrated anti-lymphoma activity in-vivo.

Antibody-drug Conjugates

IMMU-110

hLL1-Dox: Milatuzumab has been linked to doxorubicin to form an antibody-drug conjugate or ADC (known as hLL1-Dox or IMMU-110) for treatment of relapsed multiple myeloma. A Phase I/II clinical trial to evaluate this milatuzumab-doxorubicin conjugate began in 2010,^[5]^[6] but was terminated in 2021 due to lack of efficacy.^[7]

References

^ Stein R, Mattes MJ, Cardillo TM, Hansen HJ, Chang CH, Burton J, et al. (September 2007). "CD74: a new candidate target for the immunotherapy of B-cell neoplasms". Clinical Cancer Research. 13 (18 Pt 2): 5556s–5563s. doi:10.1158/1078-0432.CCR-07-1167. PMID 17875789. S2CID 23818626.
^ Alinari L, Yu B, Christian BA, Yan F, Shin J, Lapalombella R, et al. (April 2011). "Combination anti-CD74 (milatuzumab) and anti-CD20 (rituximab) monoclonal antibody therapy has in vitro and in vivo activity in mantle cell lymphoma". Blood. 117 (17): 4530–4541. doi:10.1182/blood-2010-08-303354. PMC 3099572. PMID 21228331.
^ Berkova Z, Tao RH, Samaniego F (January 2010). "Milatuzumab - a promising new immunotherapeutic agent". Expert Opinion on Investigational Drugs. 19 (1): 141–9. doi:10.1517/13543780903463854. PMID 19968579. S2CID 207475327.
^ Anti-CD74 antibody-doxorubicin conjugate, IMMU-110, in a human multiple myeloma xenograft and in monkeys. P. Sapra, R. Stein, J. Pickett, Z. Qu, S.V. Govindan, T.M. Cardillo, H.J. Hansen, I.D. Horak, G.L. Griffiths, D.M. Goldenberg. Clin Cancer Res 11:5257-5264, 2005.
^ "Milatuzumab-Doxorubicin (IMMU-110 / hLL1-dox) Clinical Trials". ADC Review / Journal of Antibody-drug Conjugates.
^ "Immunomedics initiates dosing in milatuzumab-doxorubicin conjugate Phase I/II trial for relapsed multiple myeloma". News Medical and Immunomedics Press Release. 16 June 2010.
^ Clinical trial number NCT01101594 for "A Phase I/II Study of hLL1-DOX (Milatuzumab-Doxorubicin Antibody-Drug Conjugate) in Patients With Multiple Myeloma" at ClinicalTrials.gov

Monoclonal antibodies for tumors

Tumor

Human	Adecatumumab^§ Amivantamab Ascrinvacumab^§ Atezolizumab Balstilimab^† Botensilimab Cixutumumab^§ Conatumumab^§ Daratumumab Drozitumab^§ Duligotumab^§ Dusigitumab^§ Enfortumab vedotin Enoticumab^§ Figitumumab^§ Flanvotumab^§ Ganitumab^† Glembatumumab vedotin^† Intetumumab^§ Ipilimumab Iratumumab^§ Istiratumab Icrucumab^§ Lexatumumab^§ Lucatumumab^§ Mapatumumab^§ Narnatumab^§ Necitumumab Nesvacumab^§ Nivolumab^# Ofatumumab Olaratumab^† Panitumumab Patritumab^§ Pembrolizumab^# Pritumumab^§ Radretumab^§ Ramucirumab Rilotumumab^† Robatumumab^§ Seribantumab^§ Tarextumab^§ Tisotumab vedotin Teprotumumab^† Tovetumab^§ Vantictumab^§ Votumumab^§ Zalutumumab^†
Mouse	Abagovomab Altumomab pentetate Anatumomab mafenatox Arcitumomab Bectumomab Blinatumomab Capromab pendetide Detumomab Edrecolomab Ibritumomab tiuxetan Igovomab Lilotomab Minretumomab Mitumomab Nacolomab tafenatox Moxetumomab pasudotox Naptumomab estafenatox Oregovomab Pemtumomab^† Racotumomab Satumomab pendetide Solitomab Taplitumomab paptox Nofetumomab merpentan Pintumomab Tenatumomab Tositumomab
Chimeric	Amatuximab^§ Bavituximab^§ Brentuximab vedotin Carotuximab^† Cetuximab Derlotuximab biotin^§ Dinutuximab Ecromeximab^§ Ensituximab^§ Futuximab^§ Girentuximab^† Indatuximab ravtansine^§ Isatuximab Loncastuximab tesirine Margetuximab Mirvetuximab soravtansine Rituximab^# Siltuximab Ublituximab
Humanized	Abituzumab^§ Alemtuzumab Belantamab mafodotin Bevacizumab Bivatuzumab mertansine^§ Brontictuzumab^§ Cantuzumab mertansine^§ Cantuzumab ravtansine^§ Cirmtuzumab Citatuzumab bogatox^§ Clivatuzumab tetraxetan Cofetuzumab pelidotin Dacetuzumab^§ Demcizumab^§ Dalotuzumab^§ Denintuzumab mafodotin^§ Elotuzumab Emactuzumab Emibetuzumab^§ Enoblituzumab^§ Epcoritamab Etaracizumab^§ Farletuzumab^§ Ficlatuzumab^§ Flotetuzumab^§ Gemtuzumab ozogamicin Glofitamab Imgatuzumab^§ Inotuzumab ozogamicin Labetuzumab^§ Lifastuzumab vedotin^§ Lintuzumab^§ Lorvotuzumab mertansine^§ Lumretuzumab^§ Matuzumab^§ Milatuzumab^§ Naxitamab Nimotuzumab^† Obinutuzumab Ocaratuzumab^§ Otlertuzumab^§ Onartuzumab^§ Oportuzumab monatox^† Parsatuzumab^§ Pertuzumab Pinatuzumab vedotin^§ Polatuzumab vedotin Rosmantuzumab Rovalpituzumab tesirine^† Sacituzumab govitecan Sibrotuzumab^§ Simtuzumab^§ Sofituzumab vedotin^§ Tacatuzumab tetraxetan^§ Tigatuzumab^§ Trastuzumab^# (+deruxtecan / +emtansine) Tucotuzumab celmoleukin^§ Vandortuzumab vedotin^§ Vanucizumab^§ Veltuzumab^§ Vorsetuzumab mafodotin^§
Rat/mouse hybrid	Catumaxomab Ertumaxomab^§
Chimeric + humanized	Depatuxizumab mafodotin^† Duvortuxizumab Ontuxizumab^§

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III

This page was last edited on 26 September 2023, at 14:22

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