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Francesco Bertoni, Anastasios Stathis
No abstract text is available yet for this article.
December 29, 2016: Blood
Tadeusz Robak, Andrzej Hellmann, Janusz Kloczko, Javier Loscertales, Ewa Lech-Maranda, John M Pagel, Anthony Mato, John C Byrd, Farrukh T Awan, Holger Hebart, Jose A Garcia-Marco, Brian T Hill, Michael Hallek, Amy J Eisenfeld, Scott C Stromatt, Ulrich Jaeger
Otlertuzumab (TRU-016) is a humanized anti-CD37 protein therapeutic that triggers direct caspase-independent apoptosis of malignant B cells and induces antibody-dependent cell-mediated cytotoxicity. Patients with relapsed chronic lymphocytic leukaemia (CLL) received either otlertuzumab (20 mg/kg) weekly by IV infusion for two 28-day cycles then every 14 days for four 28-day cycles and IV bendamustine (70 mg/m(2) ) on Days 1 and 2 of each cycle for up to six 28-day cycles or bendamustine alone. Thirty-two patients were treated with otlertuzumab and bendamustine and 33 with bendamustine alone...
December 15, 2016: British Journal of Haematology
Xiao-Lin Li, Ci-Xian Zhang
Chronic lymphocytic leukemia (CLL) is considered incurable despite advances in management strategies. New drugs targeting cell pathways are currently being developed for the efficient management of CLL. Various strategies involving different targets have been developed, or are currently in the developing stage. A search was conducted in the electronic database PubMed, for pre-clinical as well as clinically controlled trials reporting various strategies against CLL currently under investigation. Novel strategies included use of antibodies, small cell inhibitors, such as spleen tyrosine kinase, LYN, cyclin-dependent kinase, and histone deacetylase inhibitors...
November 2016: Oncology Letters
S Betrian, L Ysebaert, K H Heider, J P Delord, J J Fournié, A Quillet-Mary
No abstract text is available yet for this article.
November 11, 2016: Blood Cancer Journal
Zijun Y Xu-Monette, Ling Li, John C Byrd, Kausar J Jabbar, Ganiraju C Manyam, Charlotte Maria de Winde, Michiel van den Brand, Alexandar Tzankov, Carlo Visco, Jing Wang, Karen Dybkaer, April Chiu, Attilio Orazi, Youli Zu, Govind Bhagat, Kristy L Richards, Eric D Hsi, William W L Choi, Jooryung Huh, Maurilio Ponzoni, Andrés J M Ferreri, Michael B Møller, Ben M Parsons, Jane N Winter, Michael Wang, Frederick B Hagemeister, Miguel A Piris, J Han van Krieken, L Jeffrey Medeiros, Yong Li, Annemiek B van Spriel, Ken H Young
CD37 (tetraspanin TSPAN26) is a B-cell surface antigen widely expressed on mature B cells. CD37 is involved in immune regulation and tumor suppression but its function has not been fully elucidated. We assessed CD37 expression in de novo diffuse large B-cell lymphoma (DLBCL), and investigated its clinical and biologic significance in 773 patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and 231 patients treated with CHOP. We found that CD37 loss (CD37(-)) in ∼60% of DLBCL patients showed significantly decreased survival after R-CHOP treatment, independent of the International Prognostic Index (IPI), germinal center B-cell-like (GCB)/activated B-cell-like (ABC) cell of origin, nodal/extranodal primary origin, and the prognostic factors associated with CD37(-), including TP53 mutation, NF-κB(high), Myc(high), phosphorylated STAT3(high), survivin(high), p63(-), and BCL6 translocation...
December 29, 2016: Blood
Luciana De Luca, Giovanni D'Arena, Vittorio Simeon, Stefania Trino, Ilaria Laurenzana, Antonella Caivano, Francesco La Rocca, Oreste Villani, Giovanna Mansueto, Silvia Deaglio, Idanna Innocenti, Luca Laurenti, Stefano Molica, Giuseppe Pietrantuono, Angelo De Stradis, Luigi Del Vecchio, Pellegrino Musto
Microvescicles (MV) are shedding particles released by normal and neoplastic cells, whose levels in biological fluids highlight their potential role as disease biomarkers and therapeutic targets. By analyzing 131 newly diagnosed chronic lymphocytic leukemia (CLL), we found that the absolute number of serum CLL MV was significantly higher than in controls, in particular in advanced stages of disease. In addition, CD19 + and CD37+, B-cell derived MV, significantly correlated with high tumor burden. Absolute MV number cutoff selected by ROC analysis distinguished Rai stage 0 patients with shorter time to treatment (TTT) from those with more stable disease...
October 14, 2016: Leukemia & Lymphoma
Johan Blakkisrud, Ayca Løndalen, Jostein Dahle, Simon Turner, Harald Holte, Arne Kolstad, Caroline Stokke
: Red marrow (RM) is often the primary organ at risk in radioimmunotherapy; irradiation of marrow may induce short- and long-term hematologic toxicity. (177)Lu-lilotomab satetraxetan is a novel anti-CD37 antibody-radionuclide conjugate currently in phase 1/2a. Two predosing regimens have been investigated, one with 40 mg of unlabeled lilotomab antibody (arm 1) and one without (arm 2). The aim of this work was to compare RM-absorbed doses for the two arms and to correlate absorbed doses with hematologic toxicity...
January 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Johan Blakkisrud, Ayca Løndalen, Anne C T Martinsen, Jostein Dahle, Jon E Holtedahl, Tore Bach-Gansmo, Harald Holte, Arne Kolstad, Caroline Stokke
: (177)Lu-lilotomab satetraxetan is a novel antibody radionuclide conjugate currently tested in a phase 1/2a first-in-human dosage escalation trial for patients with relapsed CD37+ indolent non-Hodgkin lymphoma. The aim of this work was to develop dosimetric methods and calculate tumor-absorbed radiation doses for patients treated with (177)Lu-lilotomab satetraxetan. METHODS: Patients were treated at escalating injected activities (10, 15 and 20 MBq/kg) of (177)Lu-lilotomab satetraxetan and with different predosing, with or without 40 mg of unlabeled lilotomab...
January 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Tadeusz Robak, Jerzy Z Blonski, Pawel Robak
The development of non-chemotherapeutic agents, including monoclonal antibodies (mAbs) and other targeted drugs, makes chemotherapy-free treatment an attractive option for chronic lymphocytic leukemia (CLL). The classical mAb, rituximab, has been authorized for use in both first-line and second-line therapy for CLL. New mAbs directed against CD20, ofatumumab, and obinutuzumab (GA-101) have also been approved for the treatment of this disease. Recently, several new mAbs with potential benefits over the approved anti-CD20 antibodies have been developed for use in CLL...
April 2016: Seminars in Oncology
Xiaoping Zhang, Xueying Song, Peng Su, Meng Gou, Hao Wang, Xin Liu, Qingwei Li
CD82, a member of the tetraspanins, is originally identified as an accessory molecule in T cell activation, and it participates in the formation of immune synapse both in T cells and antigen-presenting cells of jawed vertebrates. In the present study, a CD82 homologous complementary DNA (cDNA) sequence is identified in the lamprey Lampetra japonica. The open reading frame of this sequence is 801 bp long and encodes a 266-amino acid protein. The multialignment of this sequence with several typical CD82s and CD37s of jawed vertebrates shows that it also possesses their conserved four transmembrane domains and a six-cysteine motif Cys-Cys-Gly…Cys-Ser-Cys…Cys…Cys, which is a characteristic motif of CD82 and CD37 vertebrate tetraspanin sequences...
March 2016: Development Genes and Evolution
Charlotte M de Winde, Sharon Veenbergen, Ken H Young, Zijun Y Xu-Monette, Xiao-Xiao Wang, Yi Xia, Kausar J Jabbar, Michiel van den Brand, Alie van der Schaaf, Suraya Elfrink, Inge S van Houdt, Marion J Gijbels, Fons A J van de Loo, Miranda B Bennink, Konnie M Hebeda, Patricia J T A Groenen, J Han van Krieken, Carl G Figdor, Annemiek B van Spriel
Worldwide, B cell non-Hodgkin lymphoma is the most common hematological malignancy and represents a substantial clinical problem. The molecular events that lead to B cell lymphoma are only partially defined. Here, we have provided evidence that deficiency of tetraspanin superfamily member CD37, which is important for B cell function, induces the development of B cell lymphoma. Mice lacking CD37 developed germinal center-derived B cell lymphoma in lymph nodes and spleens with a higher incidence than Bcl2 transgenic mice...
February 2016: Journal of Clinical Investigation
Eleanor L Jones, Janet L Wee, Maria C Demaria, Jessica Blakeley, Po Ki Ho, Javier Vega-Ramos, Jose A Villadangos, Annemiek B van Spriel, Michael J Hickey, Günther J Hämmerling, Mark D Wright
This study supports a new concept where the opposing functions of the tetraspanins CD37 and CD82 may coordinate changes in migration and Ag presentation during dendritic cell (DC) activation. We have previously published that CD37 is downregulated upon monocyte-derived DC activation, promotes migration of both skin and bone marrow-derived dendritic cells (BMDCs), and restrains Ag presentation in splenic and BMDCs. In this article, we show that CD82, the closest phylogenetic relative to CD37, appears to have opposing functions...
February 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Chia-Yi Hou, John Han-You Lin, Shih-Jie Lin, Wan-Ching Kuo, Han-Tso Lin
Tetraspanins are a group of cell surface molecules involved in cell adhesion, motility, metastasis, signal transduction, and immune cell activation. Members of the tetraspanin family include CD9, CD37, CD63, CD53, and others. However, few tetraspanins have been investigated in teleosts. In this study, we obtained the open reading frame of CD53 cDNA from orange spotted grouper (Epinephelus coioices), an economically important fish. The predicted amino acid structure contains four membrane-spanning domains and a conserved CCG motif...
April 2016: Fish & Shellfish Immunology
Janet L Wee, Keith E Schulze, Eleanor L Jones, Louisa Yeung, Qiang Cheng, Candida F Pereira, Adam Costin, Georg Ramm, Annemiek B van Spriel, Michael J Hickey, Mark D Wright
Deciphering the molecular basis of leukocyte recruitment is critical to the understanding of inflammation. In this study, we investigated the contribution of the tetraspanin CD37 to this key process. CD37-deficient mice showed impaired neutrophil recruitment in a peritonitis model. Intravital microscopic analysis indicated that the absence of CD37 impaired the capacity of leukocytes to follow a CXCL1 chemotactic gradient accurately in the interstitium. Moreover, analysis of CXCL1-induced leukocyte-endothelial cell interactions in postcapillary venules revealed that CXCL1-induced neutrophil adhesion and transmigration were reduced in the absence of CD37, consistent with a reduced capacity to undergo β2 integrin-dependent adhesion...
December 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Keshan Zhang, Song Zhao, Yuankai Wang, Xuejun Zhu, Hong Shen, Yugen Chen, Xingmin Sun
Clostridium difficile CD37, a clinical isolate from the USA, does not produce toxin A, B or binary toxin. The aim of this study was to determine whether strain CD37 can protect mice against infection from a challenge with a toxigenic C. difficile strain. Three groups of mice (n = 10) were pretreated with a antibiotics cocktail for 5 days, switched to sterile water for 2 days, and given one dose of clindamycin (10 mg/kg) one day (day-1) before challenge (day 0) with a toxigenic C. difficile strain. Group 1 (CD37 + UK6) was given 10(7)C...
December 2015: Anaerobe
Amitkumar Mehta, Andres Forero-Torres
Rituximab, a monoclonal antibody (MAb) against CD20, was the first MAb approved by the US Food and Drug Administration (FDA) for treatment of B cell non-Hodgkin lymphoma (B-NHL). Conjugating toxins to MAb was a technical challenge; however, with improvements in linker technology, immunoconjugates were constructed and revolutionized cancer treatment. Gemtuzumab ozogamicin was the first antibody drug conjugate (ADC) approved by the FDA. Because of the success of brentuximab vedotin and ado-trastuzumab emtansine in treating Hodgkin lymphoma (HL) and HER2-positive breast cancer, respectively, newer ADCs are being investigated...
September 2015: Current Oncology Reports
Malou Zuidscherwoude, Fabian Göttfert, Vera Marie E Dunlock, Carl G Figdor, Geert van den Bogaart, Annemiek B van Spriel
The spatial organization of membrane proteins in the plasma membrane is critical for signal transduction, cell communication and membrane trafficking. Tetraspanins organize functional higher-order protein complexes called 'tetraspanin-enriched microdomains (TEMs)' via interactions with partner molecules and other tetraspanins. Still, the nanoscale organization of TEMs in native plasma membranes has not been resolved. Here, we elucidated the size, density and distribution of TEMs in the plasma membrane of human B cells and dendritic cells using dual color stimulated emission depletion (STED) microscopy...
2015: Scientific Reports
Wenjun Tang, Chonglin Zhang, Fangfang Lu, Juan Tang, Yu Lu, Xiu Cui, Xue Qin, Shan Li
BACKGROUND AND AIMS: Thalassemia is one of the most frequent hereditary hemoglobin (Hb) disorders in southern China. Accurate population frequency data are needed for planning the control of thalassemia in the high-risk Guilin, the southern region of China. METHODS: Anemia patients (n=11,143) from the Guilin Region of the Guangxi Zhuang Autonomous Region of southern China were analyzed by Gap-PCR, PCR-based reverse dot blot (RDB), and direct sequencing methods. RESULTS: Of these patients, 4365 (39...
November 2015: Clinical Biochemistry
Ada H V Repetto-Llamazares, Roy H Larsen, Sebastian Patzke, Karianne G Fleten, David Didierlaurent, Alexandre Pichard, Jean Pierre Pouget, Jostein Dahle
177Lu-DOTA-HH1 (177Lu-HH1) is a novel anti-CD37 radioimmunoconjugate developed to treat non-Hodgkin lymphoma. Mice with subcutaneous Ramos xenografts were treated with different activities of 177Lu-HH1, 177Lu-DOTA-rituximab (177Lu-rituximab) and non-specific 177Lu-DOTA-IgG1 (177Lu-IgG1) and therapeutic effect and toxicity of the treatment were monitored. Significant tumor growth delay and increased survival of mice were observed in mice treated with 530 MBq/kg 177Lu-HH1 as compared with mice treated with similar activities of 177Lu-rituximab or non-specific 177Lu-IgG1, 0...
2015: PloS One
Charlotte M de Winde, Malou Zuidscherwoude, Angela Vasaturo, Alie van der Schaaf, Carl G Figdor, Annemiek B van Spriel
Multispectral imaging is a novel microscopy technique that combines imaging with spectroscopy to obtain both quantitative expression data and tissue distribution of different cellular markers. Tetraspanins CD37 and CD53 are four-transmembrane proteins involved in cellular and humoral immune responses. However, comprehensive immunohistochemical analyses of CD37 and CD53 in human lymphoid organs have not been performed so far. We investigated CD37 and CD53 protein expression on primary human immune cell subsets in blood and in primary and secondary lymphoid organs...
August 2015: Histochemistry and Cell Biology
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