Monoclonal antibodies targeting <scp>CD</scp>38 in hematological malignancies and beyond

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

doi:10.1111/imr.12389

Cited by 290 publications

(205 citation statements)

References 159 publications

Supporting

Mentioning

187

Contrasting

Unclassified

Order By: Relevance

“…The anti-CD38 monoclonal antibody daratumumab has shown a favorable safety profile and encouraging efficacy in patients with refractory multiple myeloma (25)(26)(27), and the anti-CD38 SAR650984 is being examined as a treatment for CD38 ϩ hematological malignancies, including AML (clinicaltrials.gov registration NCT01084252). Here, we have found that treatment of AML cell lines and primary AML apheresis samples with IFN␥ leads to the up-regulation of M1-related markers and of the daratumumab target CD38.…”

mentioning

confidence: 99%

Interferon-γ Promotes Antibody-mediated Fratricide of Acute Myeloid Leukemia Cells

Fatehchand¹,

McMichael²,

Reader³

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Edited by Peter CresswellAcute myeloid leukemia (AML) is characterized by the proliferation of immature myeloid lineage blasts. Due to its heterogeneity and to the high rate of acquired drug resistance and relapse, new treatment strategies are needed. Here, we demonstrate that IFN␥ promotes AML blasts to act as effector cells within the context of antibody therapy. Treatment with IFN␥ drove AML blasts toward a more differentiated state, wherein they showed increased expression of the M1-related markers HLA-DR and CD86, as well as of Fc␥RI, which mediates effector responses to therapeutic antibodies. Importantly, IFN␥ was able to up-regulate CD38, the target of the therapeutic antibody daratumumab. Because the antigen (CD38) and effector receptor (Fc␥RI) were both simultaneously up-regulated on the AML blasts, we tested whether IFN␥ treatment of the AML cell lines THP-1 and MV4-11 could stimulate them to target one another after the addition of daratumumab. Results showed that IFN␥ significantly increased daratumumab-mediated cytotoxicity, as measured both by 51 Cr release and lactate dehydrogenase release assays. We also found that the combination of IFN␥ and activation of Fc␥R led to the release of granzyme B by AML cells. Finally, using a murine NSG model of subcutaneous AML, we found that treatment with IFN␥ plus daratumumab significantly attenuated tumor growth. Taken together, these studies show a novel mechanism of daratumumab-mediated killing and a possible new therapeutic strategy for AML.

show abstract

mentioning

confidence: 99%

Interferon-γ Promotes Antibody-mediated Fratricide of Acute Myeloid Leukemia Cells

Fatehchand¹,

McMichael²,

Reader³

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…59 Preclinical studies indicate that CD38 is a potential target for antibody therapy in CD38-positive hematological malignancies. 18,19 The anti-CD38 monoclonal antibody Daratumumab is approved for the treatment of multiple myeloma and is currently being assessed for CLL. Anti-CD38 monoclonal antibodies are believed to exert their antitumor activity through their Fc-dependent cytotoxic effect.…”

Section: Discussionmentioning

confidence: 99%

“…However, recent evidence indicates that they can modulate CD38 enzymatic activity by decreasing cADPR production, which may in turn lead to decreased Ca 21 mobilization and signaling. 18,60 Further characterization of CD38-dependent signaling, including the RasGRP2/Rap1 axis, is therefore important for the design of novel treatments for CD38 1 hematological diseases.…”

Section: Discussionmentioning

confidence: 99%

Anatomical Society Summer Meeting in Galway

2018

Journal of Anatomy

View full text Add to dashboard Cite

show abstract

“…39 CD38 is a 45 kDa membrane protein expressed in a number of hematological malignancies from B-lymphocyte, T-lymphocyte, and myeloid origin ( Table 1 …”

Section: Anti-cd38 Monoclonal Antibodiesmentioning

confidence: 99%

Updates in Adult Acute Lymphoblastic Leukemia—Current Status of Antigen-targeted Treatments and Immunotherapy

Thomas¹

2017

Oncology &Amp; Hematology Review (US)

View full text Add to dashboard Cite

T he outcomes of adult acute lymphoblastic leukemia (ALL) remain inferior to those observed in pediatric populations. Targeted therapy with monoclonal antibodies and immunotherapy represents the most promising new way to fight ALL without significant additive toxicity. Since the use of rituximab in combination chemoimmunotherapy for treatment of B cell lineage ALL, a number of other monoclonal antibodies are under investigation for the treatment of this disease. Deep molecular remissions with anti-CD19-and anti-CD22-directed therapy have been shown in relapsed/refractory (R/R) disease, allowing for the opportunity to transplant. Blinatumomab is the first antigen-directed treatment approved for use in R/R ALL. Adoptive cellular therapy with human T cells genetically engineered to express CD19 redirected chimeric antigen receptors (CARs) has also recently demonstrated efficacy in patients with B cell lineage ALL. In this article, we review the therapeutic implications, primary results, and current status of antigen-targeted treatments and immunotherapy in adult B cell lineage ALL. KeywordsAcute lymphoblastic leukemia, monoclonal antibodies, prognosis, blinatumomab, chimeric antigen receptor (CAR) T cells, inotuzumab ozogamicin, rituximab, epratuzumab Disclosure: Xavier Thomas has nothing to declare in relation to this article. No funding was received in the publication of this article. Compliance with Ethics:This study involves a review of the literature and did not involve any studies with human or animal subjects performed by any of the authors.Authorship: All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published.Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit. One approach to improving outcomes in adult ALL involves intensification of existing chemotherapy combinations or the addition of chemotherapeutic agents. 2 The results of allogeneic hematopoietic stem cell transplantation (HSCT) for adults with ALL in first-line therapy have also improved significantly over time, 3 but it is unlikely that the sole intensification of regimens can continue to improve prognosis substantially. Intensifying chemotherapy may reduce the incidence of resistance, but at the cost of increased toxicities. Outcomes remain particularly poor in relapsed/refractory (R/R) patients. Response rates after salvage treatment range from 18-45% and median survival times from 2-8 months, with less than 10% survival after 5 years. [4][5][6][7][8][9] In this setting, allogeneic HSCT is the only curative option, but this can only be achieved in a subgroup of patients. 4,5,8 A retrospective analysis of 1,706 adult patients with Philadelphia chromosome-neg...

show abstract

Monoclonal antibodies targeting CD38 in hematological malignancies and beyond

Cited by 290 publications

References 159 publications

Interferon-γ Promotes Antibody-mediated Fratricide of Acute Myeloid Leukemia Cells

Interferon-γ Promotes Antibody-mediated Fratricide of Acute Myeloid Leukemia Cells

Anatomical Society Summer Meeting in Galway

Updates in Adult Acute Lymphoblastic Leukemia—Current Status of Antigen-targeted Treatments and Immunotherapy

Contact Info

Product

Resources

About