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Monoclonal antibodies targeting CD 38 in hematological malignancies and beyond
Author(s) -
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.
Publication year - 2016
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12389
Subject(s) - daratumumab , antibody , antibody dependent cell mediated cytotoxicity , monoclonal antibody , cytotoxicity , epitope , immunology , biology , complement dependent cytotoxicity , cancer research , biochemistry , in vitro
Summary CD 38 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 CD 38. 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 CD 38 antibodies, including daratumumab, isatuximab, and MOR 202. Daratumumab binds a unique CD 38 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. CD 38‐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, CD 38 antibodies may have a role in the treatment of diseases beyond hematological malignancies, including solid tumors and antibody‐mediated autoimmune diseases.