What is the target of daratumumab?
['Dominantly daratumumab (anti-CD38) and elotuzumab (anti-CS1) showed extraordinary effectiveness in phase I/II trials.', 'In the last few weeks, the FDA approved three new therapies for multiple myeloma: ixazomib, the first oral proteasome inhibitor; and daratumumab and elotuzumab, two monoclonal antibodies that target CD38 and SLAMF7, respectively.', 'Of these agents, CD38-targeting antibodies have marked single agent activity in extensively pretreated MM, and preliminary results from studies with relapsed/refractory patients have shown enhanced therapeutic efficacy when daratumumab and isatuximab are combined with other agents', 'Furthermore, daratumumab, and probably also other CD38-targeting antibodies, interfere with blood compatibility testing and thereby complicate the safe release of blood products. Neutralization of the therapeutic CD38 antibody or CD38 denaturation on reagent red blood cells mitigates daratumumab interference with transfusion laboratory serologic tests. ', 'Daratumumab is a fully human anti-CD38 IgG1-κ monoclonal antibody (mAb) currently being evaluated in several Phase 2 and 3 clinical studies for the treatment of multiple myeloma (MM). ', 'In this study, we describe the cytotoxic mechanisms of action of daratumumab, a novel, high-affinity, therapeutic human mAb against a unique CD38 epitope.', 'This article focuses on the basic and clinical aspects of several emerging and promising novel MoAbs for MM, such as elotuzumab which targets CS1 and daratumumab which targets CD38.', 'Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors.', 'Daratumumab is a novel human CD38 monoclonal antibody which kills CD38+ multiple myeloma cells via antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity and apoptosis.To explore the effect of lenalidomide combined with daratumumab, we first carried out standard antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity assays in which the CD38+ multiple myeloma cell line UM-9 and primary multiple myeloma cells isolated from patients were used as target cells', 'However, we discovered, next to an expected effect of effector (natural killer cells/monocytes) to target (MM cells) ratio on ADCC, a significant association between CD38 expression and daratumumab-mediated ADCC (127 patients), as well as CDC (56 patients)', 'Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma.', 'Towards effective immunotherapy of myeloma: enhanced elimination of myeloma cells by combination of lenalidomide with the human CD38 monoclonal antibody daratumumab.', 'We studied daratumumab, a CD38-targeting, human IgG1� monoclonal antibody, in a phase 1-2 trial involving patients with relapsed myeloma or relapsed myeloma that was refractory to two or more prior lines of therapy.METHODS: In part 1, the dose-escalation phase, we administered daratumumab at doses of 0.005 to 24 mg per kilogram of body weight. ', 'Antibodies targeting CS-1 (elotuzumab) and CD38 (daratumumab) in particular are currently undergoing advanced clinical phase II/III trials.', 'In this study, we describe the cytotoxic mechanisms of action of daratumumab, a novel, high-affinity, therapeutic human mAb against a unique CD38 epitope. ', 'Daratumumab is a novel human CD38 monoclonal antibody which kills CD38+ multiple myeloma cells via antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity and apoptosis.To explore the effect of lenalidomide combined with daratumumab, we first carried out standard antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity assays in which the CD38+ multiple myeloma cell line UM-9 and primary multiple myeloma cells isolated from patients were used as target cells.', 'However, we discovered, next to an expected effect of effector (natural killer cells/monocytes) to target (MM cells) ratio on ADCC, a significant association between CD38 expression and daratumumab-mediated ADCC (127 patients), as well as CDC (56 patients).', "These mechanisms may also target nonplasma cells that express CD38, which prompted evaluation of daratumumab's effects on CD38-positive immune subpopulations.", 'In the last few weeks, the FDA approved three new therapies for multiple myeloma: ixazomib, the first oral proteasome inhibitor; and daratumumab and elotuzumab, two monoclonal antibodies that target CD38 and SLAMF7, respectively. <CopyrightInformation>©2016 American Association for Cancer Research.</C', 'This review focuses on the basic and clinical aspects of two emerging and promising novel MoAbs for MM, elotuzumab which targets CS1 and daratumumab which targets CD38.', 'In this regard, some of these novel agents seem promising, such as monoclonal antibodies (anti-CD38 - daratumumab or anti-CS1 - elotuzumab) or the kinesin protein inhibitor Arry-520.', 'This is likely to change within the next few years with a number of mAb therapies being assessed in late stage clinical trials, most notably, the anti-CS-1 mAb, elotuzumab, and the anti-CD38 mAb, daratumumab, which are currently being evaluated in Phase III clinical trials for MM.', 'CD38, a type II transmembrane glycoprotein highly expressed in hematological malignancies including multiple myeloma (MM), represents a promising target for mAb-based immunotherapy. In this study, we describe the cytotoxic mechanisms of action of daratumumab, a novel, high-affinity, therapeutic human mAb against a unique CD38 epitope.', 'CD38, a type II transmembrane glycoprotein highly expressed in hematological malignancies including multiple myeloma (MM), represents a promising target for mAb-based immunotherapy. In this study, we describe the cytotoxic mechanisms of action of daratumumab, a novel, high-affinity, therapeutic human mAb against a unique CD38 epitope. Daratumumab induced potent Ab-dependent cellular cytotoxicity in CD38-expressing lymphoma- and MM-derived cell lines as well as in patient MM cells, both with autologous and allogeneic effector cells.', 'One of novel fields for anti-MM therapeutic strategy is the development of immunotherapy using monoclonal antibodies (MoAbs) against myeloma-specific antigens. This article focuses on the basic and clinical aspects of several emerging and promising novel MoAbs for MM, such as elotuzumab which targets CS1 and daratumumab which targets CD38.', 'One of novel fields for anti-MM therapeutic strategy is the development of immunotherapy using monoclonal antibodies (MoAbs) against myeloma-specific antigens. This article focuses on the basic and clinical aspects of several emerging and promising novel MoAbs for MM, such as elotuzumab which targets CS1 and daratumumab which targets CD38. Both antigens are highly expressed in more than 90% of MM patients, and the clinical trials have shown promising anti-MM effects, especially in combination with immunomodulatory agent lenalidomide.', 'Multiple myeloma (MM) remains mostly incurable despite the recent progress in the treatment strategy. One of novel fields for anti-MM therapeutic strategy is the development of immunotherapy using monoclonal antibodies (MoAbs) against myeloma-specific antigens. This article focuses on the basic and clinical aspects of several emerging and promising novel MoAbs for MM, such as elotuzumab which targets CS1 and daratumumab which targets CD38.', 'In this study, we describe the cytotoxic mechanisms of action of daratumumab, a novel, high-affinity, therapeutic human mAb against a unique CD38 epitope. Daratumumab induced potent Ab-dependent cellular cytotoxicity in CD38-expressing lymphoma- and MM-derived cell lines as well as in patient MM cells, both with autologous and allogeneic effector cells.', 'In this study, we describe the cytotoxic mechanisms of action of daratumumab, a novel, high-affinity, therapeutic human mAb against a unique CD38 epitope. Daratumumab induced potent Ab-dependent cellular cytotoxicity in CD38-expressing lymphoma- and MM-derived cell lines as well as in patient MM cells, both with autologous and allogeneic effector cells. Daratumumab stood out from other CD38 mAbs in its strong ability to induce complement-dependent cytotoxicity in patient MM cells.', 'This article focuses on the basic and clinical aspects of several emerging and promising novel MoAbs for MM, such as elotuzumab which targets CS1 and daratumumab which targets CD38. Both antigens are highly expressed in more than 90% of MM patients, and the clinical trials have shown promising anti-MM effects, especially in combination with immunomodulatory agent lenalidomide.', 'Daratumumab is a novel human CD38 monoclonal antibody which kills CD38+ multiple myeloma cells via antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity and apoptosis.DESIGN AND METHODS: To explore the effect of lenalidomide combined with daratumumab, we first carried out standard antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity assays in which the CD38+ multiple myeloma cell line UM-9 and primary multiple myeloma cells isolated from patients were used as target cells.', 'Daratumumab stood out from other CD38 mAbs in its strong ability to induce complement-dependent cytotoxicity in patient MM cells.', 'We studied daratumumab, a CD38-targeting, human IgG1ê monoclonal antibody, in a phase 1-2 trial involving patients with relapsed myeloma or relapsed myeloma that was refractory to two or more prior lines of therapy.METHODS: In part 1, the dose-escalation phase, we administered daratumumab at doses of 0.005 to 24 mg per kilogram of body weight.', 'Collectively, our results show the versatility of daratumumab to effectively kill CD38-expressing tumor cells, including patient MM cells, via diverse cytotoxic mechanisms.', 'Amongst these antibodies, elotuzumab which targets SLAMF-7 and daratumumab which targets CD38, have been recently approved by FDA for patients with relapsed/refractory MM.', 'This review focuses on the CD38 antigen and its targeting with daratumumab and provides an update on the results of recent clinical studies involving daratumumab.', 'Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma.', 'We assessed daratumumab, a novel CD38-targeted monoclonal antibody, in patients with refractory multiple myeloma.', 'Daratumumab is a human monoclonal antibody that targets CD38, a cell surface protein that is overexpressed on multiple myeloma (MM) cells.', 'Furthermore, daratumumab, and probably also other CD38-targeting antibodies, interfere with blood compatibility testing and thereby complicate the safe release of blood products.', 'Daratumumab, a human IgGκ monoclonal antibody that targets CD38, induces direct and indirect antimyeloma activity and has shown substantial efficacy as monotherapy in heavily pretreated patients with multiple myeloma, as well as in combination with bortezomib in patients with newly diagnosed multiple myeloma.', 'Importantly, IFNγ was able to up-regulate CD38, the target of the therapeutic antibody daratumumab.']
['Daratumumab is a fully human anti-CD38 IgG1-κ monoclonal antibody. It is approved for treatment of multiple myeloma.']
['CD38']