Monoclonal antibodies targeting CD38 in hematological malignancies and beyond

Summary CD38 is a multifunctional cell surface protein that has receptor as well as enzyme functions. The protein is generally expressed at low levels on various hematological and solid tissues, while plasma cells express particularly high levels of CD38. The protein is also expressed in a subset of...

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Bibliographic Details
Published in:Immunological reviews 2016-03, Vol.270 (1), p.95-112
Main Authors: van de Donk, Niels W. C. J., Janmaat, Maarten L., Mutis, Tuna, Lammerts van Bueren, Jeroen J., Ahmadi, Tahamtan, Sasser, A. Kate, Lokhorst, Henk M., Parren, Paul W. H. I.
Format: Article
Language:English
Subjects:
ADP-ribosyl Cyclase 1 - antagonists & inhibitors
ADP-ribosyl Cyclase 1 - genetics
ADP-ribosyl Cyclase 1 - metabolism
Animals
Antibodies, Monoclonal - pharmacology
Antibodies, Monoclonal - therapeutic use
Antibodies, Monoclonal, Humanized - pharmacology
Antibodies, Monoclonal, Humanized - therapeutic use
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
cancer
CD38
Clinical Studies as Topic
Cytotoxicity, Immunologic
daratumumab
Drug Evaluation, Preclinical
Drug Resistance, Neoplasm
Gene Expression Regulation, Neoplastic - drug effects
Hematologic Neoplasms - drug therapy
Hematologic Neoplasms - genetics
Hematologic Neoplasms - immunology
Hematologic Neoplasms - metabolism
Humans
Immunomodulation - drug effects
Invited Review
Invited Reviews
isatuximab
multiple myeloma
Protein Binding
Recurrence
therapeutic antibody
Treatment Outcome
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Summary:Summary CD38 is a multifunctional cell surface protein that has receptor as well as enzyme functions. The protein is generally expressed at low levels on various hematological and solid tissues, while plasma cells express particularly high levels of CD38. The protein is also expressed in a subset of hematological tumors, and shows especially broad and high expression levels in plasma cell tumors such as multiple myeloma (MM). Together, this triggered the development of various therapeutic CD38 antibodies, including daratumumab, isatuximab, and MOR202. Daratumumab binds a unique CD38 epitope and showed strong anti‐tumor activity in preclinical models. The antibody engages diverse mechanisms of action, including complement‐dependent cytotoxicity, antibody‐dependent cellular cytotoxicity, antibody‐dependent cellular phagocytosis, programmed cell death, modulation of enzymatic activity, and immunomodulatory activity. CD38‐targeting antibodies have a favorable toxicity profile in patients, and early clinical data show a marked activity in MM, while studies in other hematological malignancies are ongoing. Daratumumab has single agent activity and a limited toxicity profile, allowing favorable combination therapies with existing as well as emerging therapies, which are currently evaluated in the clinic. Finally, CD38 antibodies may have a role in the treatment of diseases beyond hematological malignancies, including solid tumors and antibody‐mediated autoimmune diseases.
ISSN:0105-2896
1600-065X
DOI:10.1111/imr.12389