Controversy in the Use of CD38 Antibody for Treatment of Myeloma: Is High CD38 Expression Good or Bad?

Abstract:

:During a time span of just a few years, the CD38 antibody, daratumumab, has been established as one of the most important new drugs for the treatment of multiple myeloma, both in the relapsed/refractory setting and, more recently, as a first-line treatment. Although much is known about the pleiotropic modes of action of daratumumab, we are still not sure how to use it in an optimal manner. Daratumumab targets CD38 on myeloma cells and a high level of CD38 expression facilitates complement-mediated cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Since the expression of CD38 by myeloma cells is downregulated during treatment with daratumumab, it may seem reasonable to introduce a wash-out period and retreat with daratumumab at a later time point when CD38 expression has recovered in order to gain the maximum benefit of daratumumab's capacity to kill myeloma cells by CDC, ADCC and ADCP. In other aspects, CD38 seems to serve as a survival factor for myeloma cells by facilitating protective myeloma cell-stromal-cell interactions, contributing to the formation of nanotubes that transfer mitochondria from the stromal cells to myeloma cells, boosting myeloma cell proliferation and survival and by generation of immunosuppressive adenosine in the bone marrow microenvironment. In addition, continuous exposure to daratumumab may keep immune suppressor cells at a low level, which boosts the anti-tumor activity of T-cells. In fact, one may speculate if in the early phase of treatment of a myeloma patient, the debulking effects of daratumumab achieved by CDC, ADCC and ADCP are more important while at a later stage, reprogramming of the patient's own immune system and certain metabolic effects may take over and become more essential. This duality may be reflected by what we often observe when we watch the slope of the M-protein from myeloma patients responding to daratumumab: A rapid initial drop followed by a slow decline of the M-protein during several months or even years. Ongoing and future clinical trials will teach us how to use daratumumab in an optimal way.

journal_name

Cells

journal_title

Cells

authors

Plesner T,van de Donk N,Richardson PG

doi

10.3390/cells9020378

subject

Has Abstract

pub_date

2020-02-06 00:00:00

issue

2

issn

2073-4409

pii

cells9020378

journal_volume

9

pub_type

杂志文章

相关文献

Cells文献大全
  • Molecular Changes in the Non-Inflamed Terminal Ileum of Patients with Ulcerative Colitis.

    abstract::Ulcerative colitis is a chronic inflammatory disease confined to the colon. Although the etiopathogenesis remains unknown, small bowel dysfunctions like histological and permeability alterations have been described in ulcerative colitis. We evaluated the molecular gene signature in the non-inflamed terminal ileum of 3...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells9081793

    authors: Lee HS,Vancamelbeke M,Verstockt S,Wilms T,Verstockt B,Sabino J,Ferrante M,Vermeire S,Cleynen I

    更新日期:2020-07-28 00:00:00

  • Mechanism-Specific Pharmacodynamics of a Novel Complex-I Inhibitor Quantified by Imaging Reversal of Consumptive Hypoxia with [18F]FAZA PET In Vivo.

    abstract::Tumors lack a well-regulated vascular supply of O2 and often fail to balance O2 supply and demand. Net O2 tension within many tumors may not only depend on O2 delivery but also depend strongly on O2 demand. Thus, tumor O2 consumption rates may influence tumor hypoxia up to true anoxia. Recent reports have shown that m...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells8121487

    authors: Gammon ST,Pisaneschi F,Bandi ML,Smith MG,Sun Y,Rao Y,Muller F,Wong F,De Groot J,Ackroyd J,Mawlawi O,Davies MA,Gopal YNV,Di Francesco ME,Marszalek JR,Dewhirst M,Piwnica-Worms D

    更新日期:2019-11-21 00:00:00

  • Interplay between Endoplasmic Reticular Stress and Survivin in Colonic Epithelial Cells.

    abstract::Sustained endoplasmic reticular stress (ERS) is implicated in aggressive metastasis of cancer cells and increased tumor cell proliferation. Cancer cells activate the unfolded protein response (UPR), which aids in cellular survival and adaptation to harsh conditions. Inhibition of apoptosis, in contrast, is a mechanism...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells7100171

    authors: Gundamaraju R,Vemuri R,Chong WC,Myers S,Norouzi S,Shastri MD,Eri R

    更新日期:2018-10-15 00:00:00

  • Exploring the Roles of lncRNAs in GBM Pathophysiology and Their Therapeutic Potential.

    abstract::Glioblastoma (GBM) remains the most devastating primary central nervous system malignancy with a median survival of around 15 months. The past decades of research have not yielded significant advancements in the treatment of GBM. In that same time, a novel class of molecules, long non-coding RNAs (lncRNAs), has been f...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells9112369

    authors: Stackhouse CT,Gillespie GY,Willey CD

    更新日期:2020-10-28 00:00:00

  • Overexpression of α-Synuclein by Oligodendrocytes in Transgenic Mice Does Not Recapitulate the Fibrillar Aggregation Seen in Multiple System Atrophy.

    abstract::The synucleinopathy underlying multiple system atrophy (MSA) is characterized by the presence of abundant amyloid inclusions containing fibrillar α-synuclein (α-syn) aggregates in the brains of the patients and is associated with an extensive neurodegeneration. In contrast to Parkinson's disease (PD) where the patholo...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells9112371

    authors: Laferrière F,He X,Zinghirino F,Doudnikoff E,Faggiani E,Meissner WG,Bezard E,De Giorgi F,Ichas F

    更新日期:2020-10-29 00:00:00

  • CCN2 Mediates S1P-Induced Upregulation of COX2 Expression in Human Granulosa-Lutein Cells.

    abstract::CCN1 and CCN2 are members of the CCN family and play essential roles in the regulation of multiple female reproductive functions, including ovulation. Cyclooxygenase-2 (COX2) is a critical mediator of ovulation and can be induced by sphingosine-1-phosphate (S1P) through the S1P1/3-mediated Yes-associated protein (YAP)...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells8111445

    authors: Hu LL,Chang HM,Yi Y,Liu Y,Taylor EL,Zheng LP,Leung PCK

    更新日期:2019-11-15 00:00:00

  • GSK-3β at the Crossroads in Regulating Protein Synthesis and Lipid Deposition in Zebrafish.

    abstract::In this study, the mechanism by which GSK-3β regulates protein synthesis and lipid deposition was investigated in zebrafish (Danio rerio). The vector of pEGFP-N1-GSK-3β was constructed and injected into the muscle of zebrafish. It was found that the mRNA and protein expression of tuberous sclerosis complex 2 (TSC2) wa...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells8030205

    authors: Gu Y,Gao L,Han Q,Li A,Yu H,Liu D,Pang Q

    更新日期:2019-02-28 00:00:00

  • Cell Mechanics in Embryoid Bodies.

    abstract::Embryoid bodies (EBs) resemble self-organizing aggregates of pluripotent stem cells that recapitulate some aspects of early embryogenesis. Within few days, the cells undergo a transition from rather homogeneous epithelial-like pluripotent stem cell colonies into a three-dimensional organization of various cell types w...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells9102270

    authors: Zeevaert K,Elsafi Mabrouk MH,Wagner W,Goetzke R

    更新日期:2020-10-11 00:00:00

  • Extracellular Matrix Structure and Composition in the Early Four-Chambered Embryonic Heart.

    abstract::During embryonic development, the heart undergoes complex morphogenesis from a liner tube into the four chambers consisting of ventricles, atria and valves. At the same time, the cardiomyocytes compact into a dense, aligned, and highly vascularized myocardium. The extracellular matrix (ECM) is known to play an importa...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells9020285

    authors: Jallerat Q,Feinberg AW

    更新日期:2020-01-24 00:00:00

  • Glaucoma: A Degenerative Optic Neuropathy Related to Neuroinflammation?

    abstract::Glaucoma is one of the leading causes of irreversible blindness in the world and remains a major public health problem. To date, incomplete knowledge of this disease's pathophysiology has resulted in current therapies (pharmaceutical or surgical) unfortunately having only a slowing effect on disease progression. Recen...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells9030535

    authors: Mélik Parsadaniantz S,Réaux-le Goazigo A,Sapienza A,Habas C,Baudouin C

    更新日期:2020-02-25 00:00:00

  • GABAB Receptors Augment TRPC3-Mediated Slow Excitatory Postsynaptic Current to Regulate Cerebellar Purkinje Neuron Response to Type-1 Metabotropic Glutamate Receptor Activation.

    abstract::During strong parallel fiber stimulation, glutamate released at parallel fiber-Purkinje cell synapses activates type-1 metabotropic glutamate receptor (mGluR1) to trigger a slow excitatory postsynaptic current (sEPSC) in cerebellar Purkinje neurons. The sEPSC is mediated by transient receptor potential canonical 3 (TR...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells7080090

    authors: Tian J,Zhu MX

    更新日期:2018-07-29 00:00:00

  • Gene Expression Profiling of NFATc1-Knockdown in RAW 264.7 Cells: An Alternative Pathway for Macrophage Differentiation.

    abstract::NFATc1, which is ubiquitous in many cell types, is the master regulator of osteoclastogenesis. However, the molecular mechanisms by which NFATc1 drives its transcriptional program to produce osteoclasts from macrophages (M) remains poorly understood. We performed quantitative PCR (QPCR) arrays and bioinformatic analys...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells8020131

    authors: Russo R,Mallia S,Zito F,Lampiasi N

    更新日期:2019-02-07 00:00:00

  • Genetic Variation Underpinning ADHD Risk in a Caribbean Community.

    abstract::Attention Deficit Hyperactivity Disorder (ADHD) is a highly heritable and prevalent neurodevelopmental disorder that frequently persists into adulthood. Strong evidence from genetic studies indicates that single nucleotide polymorphisms (SNPs) harboured in the ADGRL3 (LPHN3), SNAP25, FGF1, DRD4, and SLC6A2 genes are a...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells8080907

    authors: Puentes-Rozo PJ,Acosta-López JE,Cervantes-Henríquez ML,Martínez-Banfi ML,Mejia-Segura E,Sánchez-Rojas M,Anaya-Romero ME,Acosta-Hoyos A,García-Llinás GA,Mastronardi CA,Pineda DA,Castellanos FX,Arcos-Burgos M,Vélez JI

    更新日期:2019-08-16 00:00:00

  • PPAR-Mediated Toxicology and Applied Pharmacology.

    abstract::Peroxisome proliferator-activated receptors (PPARs), members of the nuclear hormone receptor family, attract wide attention as promising therapeutic targets for the treatment of multiple diseases, and their target selective ligands were also intensively developed for pharmacological agents such as the approved drugs f...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells9020352

    authors: Xi Y,Zhang Y,Zhu S,Luo Y,Xu P,Huang Z

    更新日期:2020-02-03 00:00:00

  • High Dose Ifosfamide in Relapsed and Unresectable High-Grade Osteosarcoma Patients: A Retrospective Series.

    abstract::Background: The evidence on high-dose ifosfamide (HD-IFO) use in patients with relapsed osteosarcoma is limited. We performed a retrospective study to analyze HD-IFO activity. Methods: Patients with osteosarcoma relapsed after standard treatment [methotrexate, doxorubicin, cisplatin +/- ifosfamide (MAP+/-I)] with meas...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells9112389

    authors: Palmerini E,Setola E,Grignani G,D'Ambrosio L,Comandone A,Righi A,Longhi A,Cesari M,Paioli A,Hakim R,Pierini M,Marchesi E,Vanel D,Pignochino Y,Donati DM,Picci P,Ferrari S

    更新日期:2020-10-31 00:00:00

  • A New Highlight of Ephedra alata Decne Properties as Potential Adjuvant in Combination with Cisplatin to Induce Cell Death of 4T1 Breast Cancer Cells In Vitro and In Vivo.

    abstract::Despite major advances in the last 10 years, whether in terms of prevention or treatment, the 5 year survival rate remains relatively low for a large number of cancers. These therapeutic failures can be the consequence of several factors associated with the cellular modifications or with the host by itself, especially...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells9020362

    authors: Sioud F,Amor S,Toumia IB,Lahmar A,Aires V,Chekir-Ghedira L,Delmas D

    更新日期:2020-02-04 00:00:00

  • Genetic Diversity and Differentiation at Structurally Varying MHC Haplotypes and Microsatellites in Bottlenecked Populations of Endangered Crested Ibis.

    abstract::Investigating adaptive potential and understanding the relative roles of selection and genetic drift in populations of endangered species are essential in conservation. Major histocompatibility complex (MHC) genes characterized by spectacular polymorphism and fitness association have become valuable adaptive markers. ...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells8040377

    authors: Lan H,Zhou T,Wan QH,Fang SG

    更新日期:2019-04-25 00:00:00

  • The Emerging Role and Promise of Circular RNAs in Obesity and Related Metabolic Disorders.

    abstract::Circular RNAs (circRNAs) are genome transcripts that are produced from back-splicing of specific regions of pre-mRNA. These single-stranded RNA molecules are widely expressed across diverse phyla and many of them are stable and evolutionary conserved between species. Growing evidence suggests that many circRNAs functi...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells9061473

    authors: Zaiou M

    更新日期:2020-06-16 00:00:00

  • miR-22-3p Negatively Affects Tumor Progression in T-Cell Acute Lymphoblastic Leukemia.

    abstract::T-cell acute lymphoblastic leukemia (T-ALL) is a rare, aggressive disease arising from T-cell precursors. NOTCH1 plays an important role both in T-cell development and leukemia progression, and more than 60% of human T-ALLs harbor mutations in components of the NOTCH1 signaling pathway, leading to deregulated cell gro...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells9071726

    authors: Saccomani V,Grassi A,Piovan E,Bongiovanni D,Di Martino L,Minuzzo S,Tosello V,Zanovello P

    更新日期:2020-07-18 00:00:00

  • 3D Printed Conductive Nanocellulose Scaffolds for the Differentiation of Human Neuroblastoma Cells.

    abstract::We prepared cellulose nanofibrils-based (CNF), alginate-based and single-walled carbon nanotubes (SWCNT)-based inks for freeform reversible embedding hydrogel (FRESH) 3D bioprinting of conductive scaffolds. The 3D printability of conductive inks was evaluated in terms of their rheological properties. The differentiati...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells9030682

    authors: Bordoni M,Karabulut E,Kuzmenko V,Fantini V,Pansarasa O,Cereda C,Gatenholm P

    更新日期:2020-03-11 00:00:00

  • Keap1-Nrf2 Pathway Regulates ALDH and Contributes to Radioresistance in Breast Cancer Stem Cells.

    abstract::Tumor recurrence after radiotherapy due to the presence of breast cancer stem cells (BCSCs) is a clinical challenge, and the mechanism remains unclear. Low levels of ROS and enhanced antioxidant defenses are shown to contribute to increasing radioresistance. However, the role of Nrf2-Keap1-Bach1 signaling in the radio...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells10010083

    authors: Kamble D,Mahajan M,Dhat R,Sitasawad S

    更新日期:2021-01-06 00:00:00

  • Sex Differences in Diabetes- and TGF-β1-Induced Renal Damage.

    abstract::While females are less affected by non-diabetic kidney diseases compared to males, available data on sex differences in diabetic nephropathy (DN) are controversial. Although there is evidence for an imbalance of sex hormones in diabetes and hormone-dependent mechanisms in transforming growth factor β1 (TGF-β1) signali...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells9102236

    authors: Ziller N,Kotolloshi R,Esmaeili M,Liebisch M,Mrowka R,Baniahmad A,Liehr T,Wolf G,Loeffler I

    更新日期:2020-10-03 00:00:00

  • YRNAs: New Insights and Potential Novel Approach in Head and Neck Squamous Cell Carcinoma.

    abstract::YRNAs are a class of non-coding RNAs that are components of the Ro60 ribonucleoprotein particle and are essential for initiation of DNA replication. Ro60 ribonucleoprotein particle is a target of autoimmune antibodies in patients suffering from systemic lupus erythematosus and Sjögren's syndrome. Deregulation of YRNAs...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells9051281

    authors: Guglas K,Kolenda T,Stasiak M,Kopczyńska M,Teresiak A,Ibbs M,Bliźniak R,Lamperska K

    更新日期:2020-05-21 00:00:00

  • Cell-Free microRNAs as Potential Oral Cancer Biomarkers: From Diagnosis to Therapy.

    abstract::Oral cavity cancer is the most frequent malignancy of the head and neck. Unfortunately, despite educational interventions for prevention and early diagnosis, oral cancer patients are often diagnosed in advanced stages associated with poor prognosis and life expectancy. Therefore, there is an urgent need to find noninv...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells8121653

    authors: Rapado-González Ó,López-López R,López-Cedrún JL,Triana-Martínez G,Muinelo-Romay L,Suárez-Cunqueiro MM

    更新日期:2019-12-17 00:00:00

  • The Snapdragon LATE ELONGATED HYPOCOTYL Plays A Dual Role in Activating Floral Growth and Scent Emission.

    abstract::The plant circadian clock controls a large number of internal processes, including growth and metabolism. Scent emission displays a circadian pattern in many species such as the snapdragon. Here we show that knocking down LATE ELONGATED HYPOCOTYL in Antirrhinum majus affects growth and scent emission. In order to gain...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells8080920

    authors: Terry MI,Pérez-Sanz F,Navarro PJ,Weiss J,Egea-Cortines M

    更新日期:2019-08-17 00:00:00

  • A Novel Chromosomal Translocation Identified due to Complex Genetic Instability in iPSC Generated for Choroideremia.

    abstract::Induced pluripotent stem cells (iPSCs) have revolutionized the study of human diseases as they can renew indefinitely, undergo multi-lineage differentiation, and generate disease-specific models. However, the difficulty of working with iPSCs is that they are prone to genetic instability. Furthermore, genetically unsta...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells8091068

    authors: Erkilic N,Gatinois V,Torriano S,Bouret P,Sanjurjo-Soriano C,Luca V,Damodar K,Cereso N,Puechberty J,Sanchez-Alcudia R,Hamel CP,Ayuso C,Meunier I,Pellestor F,Kalatzis V

    更新日期:2019-09-11 00:00:00

  • Cells in Cardiovascular Disease: Using Diversity to Confront Adversity.

    abstract::The present Special Issue on "Cells in Cardiovascular Disease" wants to offer a general overview of current cardiovascular research and illustrate how advances in the molecular characterization at the cellular level are providing unique insights into pathologies of the circulatory system [...]. ...

    journal_title:Cells

    pub_type: 社论

    doi:10.3390/cells9102192

    authors: Martínez-González J,García de Frutos P

    更新日期:2020-09-29 00:00:00

  • "Circulating Tumor Cells: Finding Rare Events for a Huge Knowledge of Cancer Dissemination".

    abstract::Circulating tumor cells (CTCs) as real-time liquid biopsy [...]. ...

    journal_title:Cells

    pub_type: 社论

    doi:10.3390/cells9030661

    authors: Alix-Panabières C

    更新日期:2020-03-09 00:00:00

  • Structural Similarity with Cholesterol Reveals Crucial Insights into Mechanisms Sustaining the Immunomodulatory Activity of the Mycotoxin Alternariol.

    abstract::The proliferation of molds in domestic environments can lead to uncontrolled continuous exposure to mycotoxins. Even if not immediately symptomatic, this may result in chronic effects, such as, for instance, immunosuppression or allergenic promotion. Alternariol (AOH) is one of the most abundant mycotoxins produced by...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells9040847

    authors: Del Favero G,Mayer RM,Dellafiora L,Janker L,Niederstaetter L,Dall'Asta C,Gerner C,Marko D

    更新日期:2020-03-31 00:00:00

  • A Novel Approach for Detecting Unique Variations among Infectious Bacterial Species in Endocarditic Cardiac Valve Vegetation.

    abstract::Infectious endocarditis (IE) remains one of the deadliest heart diseases with a high death rate, generally following thrombo-embolic events. Today, therapy is based on surgery and antibiotic therapy. When thromboembolic complications in IE patients persist, this is often due to our lack of knowledge regarding the path...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells9081899

    authors: Hannachi N,Lepidi H,Fontanini A,Takakura T,Bou-Khalil J,Gouriet F,Habib G,Raoult D,Camoin-Jau L,Baudoin JP

    更新日期:2020-08-13 00:00:00