Discovery, Development, and Mechanisms of Action of the Human<scp>CD38</scp>Antibody Daratumumab

Janmaat, Maarten L.; Donk, Niels W.C.J. van de; Bueren, Jeroen Lammerts van; Ahmadi, Tahamtan; Sasser, A. Kate; Jansson, Richard K.; Lokhorst, Henk M.; Parren, Paul W.H.I.

doi:10.1002/9783527808694.ch7

Cited by 3 publications

(2 citation statements)

References 128 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It leads to the generation of anaphylatoxins (C3a, C4a, and C5a), chemo-attractants, and opsonins. Additionally, terminal complement pathway activation generates membrane attack complexes (MAC), which build pores in the MM cell membrane, resulting in direct cell lysis [61,62]. The Daratumumab-mediated CDC depends on CD38 expression level, and a high CD38 expression on MM cell membranes strongly improves CDC activity of Daratumumab [63].…”

Section: Cd38 Mabs Induce Complement Dependent Cytotoxicitymentioning

confidence: 99%

Regulation of CD38 on Multiple Myeloma and NK Cells by Monoclonal Antibodies

Wu¹,

Zhao²

2022

Int. J. Biol. Sci.

View full text Add to dashboard Cite

CD38 is highly expressed on multiple myeloma (MM) cells and plays a role in regulating tumor generation and development. CD38 monoclonal antibodies (mAbs) have been used as an effective therapy for MM treatment by various mechanisms, including complement-dependent cytotoxic effects, antibodydependent cell-mediated cytotoxicity, antibody-dependent cellular phagocytosis, programmed cell death, enzymatic modulation, and immunomodulation. Although CD38 mAbs inhibit the proliferation and survival of MM cells, there are substantial side effects on antitumoral NK cells. The NK-mediated immune response needs to be further evaluated to minimize the adverse effects of NK cell loss. The killing effect of CD38 mAbs on CD38 high NK cells should be minimized and the potential combination of CD38 low/-NK cells and CD38 mAbs should be maximized to better benefit from their therapeutic efficacy against MM. CD38 mAb effects against MM can be maximized by combination therapies with immunomodulatory imide drugs (IMiDs), proteasome inhibitors (PIs), anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) antibodies, or cellular therapies for the treatment of MM, especially in patients with relapsed or refractory MM (R/R MM) and drug-resistant MM.

show abstract

Section: Cd38 Mabs Induce Complement Dependent Cytotoxicitymentioning

confidence: 99%

Regulation of CD38 on Multiple Myeloma and NK Cells by Monoclonal Antibodies

Wu¹,

Zhao²

2022

Int. J. Biol. Sci.

View full text Add to dashboard Cite

show abstract

“…The mAb DARA, specific for CD38, has proven to be moderately successful in the treatment of MM based on targeting and clearing CD38-positive MM cells [ 76 ]. However, in analogy to the action of CD20 mAbs RTX and OFA, DARA also down-regulates the expression of CD38 on targeted MM cells that are not cleared [ 77 , 78 ].…”

Section: Daratumumab Mediates Trogocytosis Of Cd38 On Numerous Cellsmentioning

confidence: 99%

FcγR-Mediated Trogocytosis 2.0: Revisiting History Gives Rise to a Unifying Hypothesis

Lindorfer

Taylor

2022

Antibodies

View full text Add to dashboard Cite

There is increasing interest in the clinical implications and immunology of trogocytosis, a process in which the receptors on acceptor cells remove and internalize cognate ligands from donor cells. We have reported that this phenomenon occurs in cancer immunotherapy, in which cells that express FcγR remove and internalize CD20 and bound mAbs from malignant B cells. This process can be generalized to include other reactions including the immune adherence phenomenon and antibody-induced immunosuppression. We discuss in detail FcγR-mediated trogocytosis and the evidence supporting a proposed predominant role for liver sinusoidal endothelial cells via the action of the inhibitory receptor FcγRIIb2. We describe experiments to test the validity of this hypothesis. The elucidation of the details of FcγR-mediated trogocytosis has the potential to allow for the development of novel therapies that can potentially block or enhance this reaction, depending upon whether the process leads to unfavorable or positive biological effects.

show abstract

Biological bases of cancer immunotherapy

Carazas

Pinto

Casado

2021

Expert Rev. Mol. Med.

View full text Add to dashboard Cite

Immunotherapy has changed the landscape of cancer treatment and has significantly improved the outcome of several cancer types including breast, lung, colorectal and prostate. Neoantigen recognition and immune checkpoint inhibitors are nowadays the milestones of different immunotherapeutic regimes; however, high cost, primary and acquired resistance and the high variability of responses make their extensive use difficult. The development of better predictive biomarkers that represent tumour diversity shows promise because there is a significant body of clinical data showing a spectrum of immunotherapeutic responses that might be related back to their specific characteristics. This article makes a conceptual and historical review to summarise the main advances in our understanding of the role of the immune system in cancer, while describing the methodological details that have been successfully implemented on cancer treatments and that may hold the key to improved therapeutic approaches.

show abstract

Discovery, Development, and Mechanisms of Action of the HumanCD38Antibody Daratumumab

Cited by 3 publications

References 128 publications

Regulation of CD38 on Multiple Myeloma and NK Cells by Monoclonal Antibodies

Regulation of CD38 on Multiple Myeloma and NK Cells by Monoclonal Antibodies

FcγR-Mediated Trogocytosis 2.0: Revisiting History Gives Rise to a Unifying Hypothesis

Biological bases of cancer immunotherapy

Contact Info

Product

Resources

About