CD38 antibodies in multiple myeloma: back to the future.

Abstract:

:CD38 is highly and uniformly expressed on multiple myeloma (MM) cells, and at relatively low levels on normal lymphoid and myeloid cells, and in some tissues of nonhematopoietic origin. CD38 is a transmembrane glycoprotein with ectoenzymatic activity, and also functions as a receptor and adhesion molecule. Altogether, this has triggered the development of several CD38 antibodies including daratumumab (fully human), isatuximab (chimeric), and MOR202 (fully human). CD38 antibodies have pleiotropic mechanisms of action including Fc-dependent immune-effector mechanisms, direct apoptotic activity, and immunomodulatory effects by the elimination of CD38+ immune-suppressor cells. CD38-targeting antibodies are generally well tolerated and induce partial response or better in ∼30% of heavily pretreated MM patients as monotherapy. Based on their distinct mechanisms of action, favorable toxicity profile, and single-agent activity, CD38 antibodies are attractive partners in combination regimens. Indeed, deep responses and prolonged progression-free survival can be achieved in relapsed/refractory MM patients when CD38 antibodies are combined with immunomodulatory agents or proteasome inhibitors. Infusion-related reactions, which typically occur during the first infusion, are the most frequent adverse events. Attention should also be paid to the interference of CD38 antibodies with certain laboratory assays, which may complicate response evaluation and blood compatibility testing. Several studies are currently examining the role of CD38-based therapies in newly diagnosed and high-risk smoldering MM. Furthermore, CD38 antibodies are currently also under investigation in other hematologic malignancies, including acute lymphoblastic leukemia, natural killer/T-cell lymphoma, and acute myeloid leukemia, as well as in solid tumors.

journal_name

Blood

journal_title

Blood

authors

van de Donk NWCJ,Richardson PG,Malavasi F

doi

10.1182/blood-2017-06-740944

subject

Has Abstract

pub_date

2018-01-04 00:00:00

pages

13-29

issue

1

eissn

0006-4971

issn

1528-0020

pii

blood-2017-06-740944

journal_volume

131

pub_type

杂志文章,评审

相关文献

BLOOD文献大全
  • Genetic correction of p67phox deficient chronic granulomatous disease using peripheral blood progenitor cells as a target for retrovirus mediated gene transfer.

    abstract::Chronic granulomatous disease (CGD) can result from any of four single gene defects involving the components of the superoxide (O-2) generating phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. We show that transduction of peripheral blood CD34+ hematopoietic progenitors from a p67phox deficient C...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Weil WM,Linton GF,Whiting-Theobald N,Vowells SJ,Rafferty SP,Li F,Malech HL

    更新日期:1997-03-01 00:00:00

  • GATA factor mutations in hematologic disease.

    abstract::GATA family proteins play essential roles in development of many cell types, including hematopoietic, cardiac, and endodermal lineages. The first three factors, GATAs 1, 2, and 3, are essential for normal hematopoiesis, and their mutations are responsible for a variety of blood disorders. Acquired and inherited GATA1 ...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2016-09-687889

    authors: Crispino JD,Horwitz MS

    更新日期:2017-04-13 00:00:00

  • A genome-wide association analysis of serum iron concentrations.

    abstract::To investigate genetic variants that affect iron concentrations in persons not affected by overt genetic disorders of iron metabolism, a genome-wide association study was conducted in the InCHIANTI Study (N = 1206) and the Baltimore Longitudinal Study of Aging (N = 713). The top 2 single-nucleotide polymorphisms were ...

    journal_title:Blood

    pub_type: 杂志文章,meta分析

    doi:10.1182/blood-2009-07-232496

    authors: Tanaka T,Roy CN,Yao W,Matteini A,Semba RD,Arking D,Walston JD,Fried LP,Singleton A,Guralnik J,Abecasis GR,Bandinelli S,Longo DL,Ferrucci L

    更新日期:2010-01-07 00:00:00

  • How we manage autologous stem cell transplantation for patients with multiple myeloma.

    abstract::An estimated 22 350 patients had multiple myeloma diagnosed in 2013, representing 1.3% of all new cancers; 10 710 deaths are projected, representing 1.8% of cancer deaths. Approximately 0.7% of US men and women will have a myeloma diagnosis in their lifetime, and with advances in therapy, 77 600 US patients are living...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2014-03-544759

    authors: Gertz MA,Dingli D

    更新日期:2014-08-07 00:00:00

  • The antitumorigenic trifecta.

    abstract::The laboratory of Judah Folkman identified the potent endogenous antiangiogenic protein angiostatin in 1994.(1) In this issue of Blood, Lee and colleagues propose 2 new mechanisms of action for angiostatin that may represent promising targets for new cancer therapeutics.(2). ...

    journal_title:Blood

    pub_type: 评论,杂志文章

    doi:10.1182/blood-2009-06-226233

    authors: Mowery YM,Pizzo SV

    更新日期:2009-08-27 00:00:00

  • Rearrangement of both immunoglobulin and T-cell receptor genes in a prolymphocytic variant of hairy cell leukemia patient resistant to interferon-alpha.

    abstract::We describe a patient with the so-called "prolymphocytic variant" form of hairy cell leukemia (HCL) resistant to treatment with interferon-alpha (IFN-alpha). Analysis of immunoglobulin (Ig) and T-cell receptor-beta (TCR beta) gene rearrangements from serial peripheral blood mononuclear cell specimens (MNCs) confirmed ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Giardina SL,Young HA,Faltynek CR,Jaffe ES,Clark JW,Steis RG,Urba WJ,Mathieson BJ,Gralnick H,Lawrence J

    更新日期:1988-11-01 00:00:00

  • Immunization with host-type CD8{alpha}+ dendritic cells reduces experimental acute GVHD in an IL-10-dependent manner.

    abstract::Little is known about the role of active immunization in suppressing undesirable immune responses. Because CD8alpha(+) dendritic cells (DCs) suppress certain immune responses, we tested the hypothesis that immunization of donors with host-derived CD8alpha(+) DCs will reduce host-specific donor T-cell responses. BALB/c...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-06-229708

    authors: Toubai T,Malter C,Tawara I,Liu C,Nieves E,Lowler KP,Sun Y,Reddy P

    更新日期:2010-01-21 00:00:00

  • Thrombosis in primary myelofibrosis: incidence and risk factors.

    abstract::We assessed frequency and predictive factors for major cardiovascular (CV) events in 707 patients with primary myelofibrosis (PMF) followed in 4 European institutions. A total of 236 deaths (33%) were recorded for an overall mortality of 7.7% patient-years (pt-yr). Fatal and nonfatal thromboses were registered in 51 (...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-08-238956

    authors: Barbui T,Carobbio A,Cervantes F,Vannucchi AM,Guglielmelli P,Antonioli E,Alvarez-Larrán A,Rambaldi A,Finazzi G,Barosi G

    更新日期:2010-01-28 00:00:00

  • Combination therapy for radiation-induced bone marrow aplasia in nonhuman primates using synthokine SC-55494 and recombinant human granulocyte colony-stimulating factor.

    abstract::Combination cytokine therapy continues to be evaluated in an effort to stimulate multilineage hematopoietic reconstitution after bone marrow myelosuppression. This study evaluated the efficacy of combination therapy with the synthetic interleukin-3 receptor agonist, Synthokine-SC55494, and recombinant methionyl human ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: MacVittie TJ,Farese AM,Herodin F,Grab LB,Baum CM,McKearn JP

    更新日期:1996-05-15 00:00:00

  • The role of sialic acid in the dysfibrinogenemia associated with liver disease: distribution of sialic acid on the constituent chains.

    abstract::To further evaluate the role of sialic acid in the dysfibrinogenemia associated with liver disease, we studied the effect of removal of excess sialic acid residues from the fibrinogen of five patients with liver disease on the thrombin time and fibrin monomer aggregation. Patient fibrinogens containing 1.4-3.4 residue...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Martinez J,MacDonald KA,Palascak JE

    更新日期:1983-06-01 00:00:00

  • Normal cycling patterns of hematopoietic stem cell subpopulations: an assay using long-term in vivo BrdU infusion.

    abstract::It was found in a long-term bromodeoxyuridine (BrdU) infusion study that two or more different subpopulations of bone marrow stem cells exist in mice. One of these subpopulations appears to be noncycling and forms approximately 10% of eight-day CFU-S. Another one, a subpopulation of slowly cycling bone marrow cells, i...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Pietrzyk ME,Priestley GV,Wolf NS

    更新日期:1985-12-01 00:00:00

  • Leukemic transformation by the APL fusion protein PRKAR1A-RAR{alpha} critically depends on recruitment of RXR{alpha}.

    abstract::PRKAR1A (R1A)-retinoic acid receptor-alpha (R1A-RARalpha) is the sixth RARalpha-containing fusion protein in acute promyelocytic leukemia (APL). Using the murine bone-marrow retroviral transduction/transformation assay, we showed that R1A-RARalpha fusion protein could transform bone-marrow progenitor/stem cells. In ge...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-07-232652

    authors: Qiu JJ,Lu X,Zeisig BB,Ma Z,Cai X,Chen S,Gronemeyer H,Tweardy DJ,So CW,Dong S

    更新日期:2010-01-21 00:00:00

  • Inhibition of the erythropoietin-induced erythroid differentiation by granulocyte-macrophage colony-stimulating factor in the human UT-7 cell line is not due to a negative regulation of the erythropoietin receptor.

    abstract::The human pluripotent UT-7 cell line is growth factor-dependent for proliferation and differentiation. We have previously shown that (1) granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (Epo) induce a myeloid and erythroid pattern of differentiation, respectively; (2) GM-CSF acts predominan...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Hermine O,Dubart A,Porteux F,Mayeux P,Titeux M,Dumenil D,Vainchenker W

    更新日期:1996-03-01 00:00:00

  • The principal results of the International Immune Tolerance Study: a randomized dose comparison.

    abstract::The International Immune Tolerance Study was a multicenter, prospective, randomized comparison of high-dose (HD; 200 IU/kg/d) and low-dose (LD; 50 IU/kg 3 times/week) factor VIII regimens in 115 "good-risk," severe high-titer inhibitor hemophilia A subjects. Sixty-six of 115 subjects reached the defined study end poin...

    journal_title:Blood

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1182/blood-2011-08-369132

    authors: Hay CR,DiMichele DM,International Immune Tolerance Study.

    更新日期:2012-02-09 00:00:00

  • Src tyrosine kinase preactivation is associated with platelet hypersensitivity in essential thrombocythemia and polycythemia vera.

    abstract::Polycythemia vera (PV) and essential thrombocythemia (ET) are chronic myeloproliferative disorders characterized by an increased incidence of thrombo-hemorrhagic complications. The acquired somatic Janus kinase 2 (JAK2) V617F mutation is present in the majority of PV and ET patients. Because aberrant protein Tyr-phosp...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-12-196535

    authors: Randi ML,Brunati AM,Scapin M,Frasson M,Deana R,Magrin E,Fabris F,Donella-Deana A

    更新日期:2010-01-21 00:00:00

  • A small molecule inhibitor of Pim protein kinases blocks the growth of precursor T-cell lymphoblastic leukemia/lymphoma.

    abstract::The serine/threonine Pim kinases are up-regulated in specific hematologic neoplasms, and play an important role in key signal transduction pathways, including those regulated by MYC, MYCN, FLT3-ITD, BCR-ABL, HOXA9, and EWS fusions. We demonstrate that SMI-4a, a novel benzylidene-thiazolidine-2, 4-dione small molecule ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-07-233445

    authors: Lin YW,Beharry ZM,Hill EG,Song JH,Wang W,Xia Z,Zhang Z,Aplan PD,Aster JC,Smith CD,Kraft AS

    更新日期:2010-01-28 00:00:00

  • Recombinant gibbon interleukin-3 acts synergistically with recombinant human G-CSF and GM-CSF in vitro.

    abstract::Recombinant gibbon interleukin-3 (IL-3) is a multilineage hematopoietic colony-stimulating factor (CSF) that recently was cloned and found to be highly homologous with human IL-3. Gibbon IL-3, as well as human granulocyte-CSF (G-CSF) and human granulocyte-macrophage CSF (GM-CSF), stimulated normal human bone marrow ce...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Paquette RL,Zhou JY,Yang YC,Clark SC,Koeffler HP

    更新日期:1988-06-01 00:00:00

  • Mucosal iron transport by rat intestine.

    abstract::Using highly sensitive 2-site immunoradiometric assays, we examined the relationship between iron absorption from closed intestinal loops and transferrin and ferritin concentrations in isolated duodenal mucosal cells. As in prior studies, mucosal ferritin correlates inversely with iron absorption and directly with bod...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Savin MA,Cook JD

    更新日期:1980-12-01 00:00:00

  • Identification of human chronic myelogenous leukemia progenitor cells with hemangioblastic characteristics.

    abstract::Overwhelming evidence from leukemia research has shown that the clonal population of neoplastic cells exhibits marked heterogeneity with respect to proliferation and differentiation. There are rare stem cells within the leukemic population that possess extensive proliferation and self-renewal capacity not found in the...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-07-2514

    authors: Fang B,Zheng C,Liao L,Han Q,Sun Z,Jiang X,Zhao RC

    更新日期:2005-04-01 00:00:00

  • MBD4 guards against methylation damage and germ line deficiency predisposes to clonal hematopoiesis and early-onset AML.

    abstract::The tendency of 5-methylcytosine (5mC) to undergo spontaneous deamination has had a major role in shaping the human genome, and this methylation damage remains the primary source of somatic mutations that accumulate with age. How 5mC deamination contributes to cancer risk in different tissues remains unclear. Genomic ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2018-05-852566

    authors: Sanders MA,Chew E,Flensburg C,Zeilemaker A,Miller SE,Al Hinai AS,Bajel A,Luiken B,Rijken M,Mclennan T,Hoogenboezem RM,Kavelaars FG,Fröhling S,Blewitt ME,Bindels EM,Alexander WS,Löwenberg B,Roberts AW,Valk PJM,Majews

    更新日期:2018-10-04 00:00:00

  • Clonal evidence for the transduction of CD34+ cells with lymphomyeloid differentiation potential and self-renewal capacity in the SCID-X1 gene therapy trial.

    abstract::Immune function has been restored in 9 of 10 children with X-linked severe combined immunodeficiency by gamma c gene transfer in CD34+ cells. The distribution of both T-cell receptor (TCR) V beta family usage and TCR V beta complementarity-determining region 3 (CDR3) length revealed a broadly diversified T-cell repert...

    journal_title:Blood

    pub_type: 临床试验,杂志文章

    doi:10.1182/blood-2004-07-2648

    authors: Schmidt M,Hacein-Bey-Abina S,Wissler M,Carlier F,Lim A,Prinz C,Glimm H,Andre-Schmutz I,Hue C,Garrigue A,Le Deist F,Lagresle C,Fischer A,Cavazzana-Calvo M,von Kalle C

    更新日期:2005-04-01 00:00:00

  • Human CD34+ hematopoietic progenitors have low, cytokine-unresponsive O6-alkylguanine-DNA alkyltransferase and are sensitive to O6-benzylguanine plus BCNU.

    abstract::Human bone marrow (BM) cells contain low levels of the DNA repair protein, O6-alkylguanine-DNA alkyltransferase, which may explain their susceptibility to nitrosourea-induced cytotoxicity and the development of secondary leukemia after nitrosourea treatment. Isolated CD34+ myeloid progenitors were also found to have l...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Gerson SL,Phillips W,Kastan M,Dumenco LL,Donovan C

    更新日期:1996-09-01 00:00:00

  • Extracellular histones induce erythrocyte fragility and anemia.

    abstract::Extracellular histones have been shown to play an important pathogenic role in many diseases, primarily through their cytotoxicity toward nucleated cells and their ability to promote platelet activation with resultant thrombosis and thrombocytopenia. In contrast, little is known about the effect of extracellular histo...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2017-06-790519

    authors: Kordbacheh F,O'Meara CH,Coupland LA,Lelliott PM,Parish CR

    更新日期:2017-12-28 00:00:00

  • Heparin and heparan sulfate bind interleukin-10 and modulate its activity.

    abstract::Glycosaminoglycans (GAG) are a group of negatively charged molecules that have been shown to bind and directly regulate the bioactivity of growth factors and cytokines such as basic fibroblast growth factor, transforming growth factor-beta, IL-7, and interferon-gamma. The ability of GAG to interact with human IL-10 (h...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Salek-Ardakani S,Arrand JR,Shaw D,Mackett M

    更新日期:2000-09-01 00:00:00

  • Cost effectiveness of caplacizumab in acquired thrombotic thrombocytopenic purpura.

    abstract::Acquired thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease characterized by thrombotic microangiopathy leading to end-organ damage. The standard of care (SOC) treatment is therapeutic plasma exchange (TPE) alongside immunomodulation with steroids, with increasing use of rituximab +/- other immuno...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.2020006052

    authors: Goshua G,Sinha P,Hendrickson JE,Tormey CA,Bendapudi P,Lee AI

    更新日期:2020-12-06 00:00:00

  • Most antiviral CD8 T cells during chronic viral infection do not express high levels of perforin and are not directly cytotoxic.

    abstract::Despite the frequency of HIV-specific CD8 T cells, most HIV-infected patients do not control viral replication without antiviral drugs. Although CD8 T cells are important in containing acute HIV and simian immunodeficiency virus (SIV) infection, CD8 T-cell functions are compromised in chronic infection. To investigate...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-03-0791

    authors: Zhang D,Shankar P,Xu Z,Harnisch B,Chen G,Lange C,Lee SJ,Valdez H,Lederman MM,Lieberman J

    更新日期:2003-01-01 00:00:00

  • Mice lacking the CCR9 CC-chemokine receptor show a mild impairment of early T- and B-cell development and a reduction in T-cell receptor gammadelta(+) gut intraepithelial lymphocytes.

    abstract::CC chemokine receptor (CCR) 9, the receptor for the CC-chemokine CCL25/thymus-expressed chemokine (TECK), is mainly expressed by thymocytes and by intraepithelial (IEL) and lamina propria lymphocytes of the small intestine. To study the biologic role of CCR9, a mouse strain was generated in which the CCR9 gene was del...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v98.9.2626

    authors: Wurbel MA,Malissen M,Guy-Grand D,Meffre E,Nussenzweig MC,Richelme M,Carrier A,Malissen B

    更新日期:2001-11-01 00:00:00

  • Anti-CD33 monoclonal antibody and etoposide/cytosine arabinoside combinations for the ex vivo purification of bone marrow in acute nonlymphocytic leukemia.

    abstract::Pharmacologic and immunologic methods of ex-vivo bone marrow (BM) purging for acute nonlymphocytic leukemia (ANLL) were combined to augment the effect of either method alone. Etoposide (VP16; 20 to 30 micrograms/mL) with or without cytosine arabinoside (Ara C; 10 mg/mL) was used in tandem with the anti-CD33 monoclonal...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Stiff PJ,Schulz WC,Bishop M,Marks L

    更新日期:1991-01-15 00:00:00

  • Downregulation of TAP1 in B lymphocytes by cellular and Epstein-Barr virus-encoded interleukin-10.

    abstract::Virally infected cells degrade intracellular viral proteins proteolytically and present the resulting peptides in association with major histocompatibility complex (MHC) class I molecules to CD8+ cytotoxic T lymphocytes (CTLs). These cells are normally prone to CTL-mediated elimination. However, several viruses have e...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Zeidler R,Eissner G,Meissner P,Uebel S,Tampé R,Lazis S,Hammerschmidt W

    更新日期:1997-09-15 00:00:00

  • Normal human serum contains natural antibodies reactive with autologous ABO blood group antigens.

    abstract::It is widely accepted that the serum of healthy individuals contains natural antibodies only against those blood group A or B antigens that are not expressed on the individual's red blood cells. The mechanisms involved in tolerance to autologous blood group antigens remain unclear. In the present study, we show that I...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Spalter SH,Kaveri SV,Bonnin E,Mani JC,Cartron JP,Kazatchkine MD

    更新日期:1999-06-15 00:00:00