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antibody multiple myeloma

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https://www.readbyqxmd.com/read/29142783/birth-order-and-maternal-age-for-reported-cases-of-severe-prenatal-cortical-hyperostosis-caffey-silverman-disease
#1
Rolf R Engel, Raul F Cifuentes
The spectrum of prenatal cortical hyperostosis includes a mild phenotype that typically presents after 35 weeks of gestation, and a severe form that presents earlier. The skeletal and systemic manifestations of the severe phenotype remain unexplained. A review of reported cases indicates that older mothers and firstborn infants are overrepresented. This combination suggests decreased fertility. Fourteen years after the birth of the present case, his mother presented with renal failure from multiple myeloma raising the possibility that a maternal antibody may play a role in the etiology of severe prenatal Caffey disease...
July 2017: American Journal of Perinatology Reports
https://www.readbyqxmd.com/read/29133623/immu-140-a-novel-sn-38-antibody-drug-conjugate-targeting-hla-dr-mediates-dual-cytotoxic-effects-in-hematological-cancers-and-malignant-melanoma
#2
Thomas M Cardillo, Serengulam V Govindan, Maria B Zalath, Diane L Rossi, Yang Wang, Chien-Hsing Chang, David M Goldenberg
HLA-DR is a member of the MHC class II antigen family expressed on hematological and solid tumors.  Antibodies directed against HLA-DR have demonstrated some clinical success, but toxicities limited development.  IMMU-140 is an anti-HLA-DR antibody-drug conjugate comprised of the active metabolite of irinotecan, SN-38, conjugated to a humanized anti-HLA-DR IgG4 antibody (IMMU-114); the IgG4 naked antibody is devoid of immune functions. Our aim was to determine if SN-38, the metabolite of a drug not commonly used in hematopoietic cancers, would be effective and safe when targeted to HLA-DR-expressing tumors...
November 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29127588/daratumumab-a-review-in-relapsed-and-or-refractory-multiple-myeloma
#3
Hannah A Blair
Intravenous daratumumab (DARZALEX(®)) is a first-in-class human IgG1κ monoclonal antibody against CD38 available for use in patients with relapsed and/or refractory multiple myeloma. In phase I/II and II trials and a pooled analysis of these studies, daratumumab monotherapy induced an overall response (partial response or better) in approximately one-third of patients; responses were rapid, deep and durable. An overall survival (OS) benefit was seen with daratumumab monotherapy, including in patients with a minimal response or stable disease...
November 10, 2017: Drugs
https://www.readbyqxmd.com/read/29118010/cd38-antibodies-in-multiple-myeloma-back-to-the-future
#4
Niels W C J van de Donk, Paul G Richardson, Fabio Malavasi
CD38 is highly and uniformly expressed on MM cells, and at relatively low levels on normal lymphoid and myeloid cells, and in some tissues of non-hematopoietic origin. CD38 is a transmembrane glycoprotein with ectoenzymatic activity, and also functions as 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-positive immunesuppressor cells...
November 8, 2017: Blood
https://www.readbyqxmd.com/read/29118005/redirecting-t-cells-to-hematological-malignancies-with-bispecific-antibodies
#5
Mireya Paulina Velasquez, Challice L Bonifant, Stephen Gottschalk
There is a need to improve outcomes for patients with recurrent and/or refractory hematological malignancies. Immunotherapy holds the promise to meet this need since it does not rely on the cytotoxic mechanism of conventional therapies. Among different forms of immunotherapy, redirecting T cells to hematological malignancies with bispecific antibodies (BsAbs) is an attractive strategy. BsAbs are an 'off-the-shelf' product that is easily scalable in contrast to adoptive T-cell therapies. Among these, the bispecific T-cell engager (BiTE) blinatumomab has emerged as the most successful BsAb to date...
November 8, 2017: Blood
https://www.readbyqxmd.com/read/29106400/the-activated-conformation-of-integrin-%C3%AE-7-is-a-novel-multiple-myeloma-specific-target-for-car-t-cell-therapy
#6
Naoki Hosen, Yukiko Matsunaga, Kana Hasegawa, Hiroshi Matsuno, Yuki Nakamura, Mio Makita, Kouki Watanabe, Mikako Yoshida, Kei Satoh, Soyoko Morimoto, Fumihiro Fujiki, Hiroko Nakajima, Jun Nakata, Sumiyuki Nishida, Akihiro Tsuboi, Yoshihiro Oka, Masahiro Manabe, Hiroyoshi Ichihara, Yasutaka Aoyama, Atsuko Mugitani, Takafumi Nakao, Masayuki Hino, Ryosuke Uchibori, Keiya Ozawa, Yoshihiro Baba, Seitaro Terakura, Naoki Wada, Eiichi Morii, Junichi Nishimura, Kiyoshi Takeda, Yusuke Oji, Haruo Sugiyama, Junichi Takagi, Atsushi Kumanogoh
Cancer-specific cell-surface antigens are ideal targets for monoclonal antibody (mAb)-based immunotherapy but are likely to have previously been identified in transcriptome or proteome analyses. Here, we show that the active conformer of an integrin can serve as a specific therapeutic target for multiple myeloma (MM). We screened >10,000 anti-MM mAb clones and identified MMG49 as an MM-specific mAb specifically recognizing a subset of integrin β7 molecules. The MMG49 epitope, in the N-terminal region of the β7 chain, is predicted to be inaccessible in the resting integrin conformer but exposed in the active conformation...
November 6, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29104288/combination-of-a-novel-hdac-6-inhibitor-acy-241-and-anti-pd-l1-antibody-enhances-anti-tumor-immunity-and-cytotoxicity-in-multiple-myeloma
#7
A Ray, D S Das, Y Song, T Hideshima, Y-T Tai, D Chauhan, K C Anderson
Leukemia accepted article preview online, 06 November 2017. doi:10.1038/leu.2017.322.
November 6, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29100408/a-novel-fc-engineered-human-icam-1-cd54-antibody-with-potent-anti-myeloma-activity-developed-by-cellular-panning-of-phage-display-libraries
#8
Katja Klausz, Michael Cieker, Christian Kellner, Hans-Heinrich Oberg, Dieter Kabelitz, Thomas Valerius, Renate Burger, Martin Gramatzki, Matthias Peipp
To identify antibodies suitable for multiple myeloma (MM) immunotherapy, a cellular screening approach was developed using plasma cell lines JK-6L and INA-6 and human synthetic single-chain fragment variable (scFv) phage libraries. Isolated phage antibodies were screened for myeloma cell surface reactivity. Due to its binding characteristics, phage PIII-15 was selected to generate the scFv-Fc fusion protein TP15-Fc with an Fc domain optimized for FcγRIIIa binding. Various MM cell lines and patient-derived CD138-positive malignant plasma cells, but not granulocytes, B or T lymphocytes from healthy donors were recognized by TP15-Fc...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29098319/-multiple-myeloma-what-has-been-confirmed-in-therapy
#9
REVIEW
M-A Baertsch, H Goldschmidt
Multiple myeloma (MM) is a malignancy of terminally differentiated B cells/plasma cells and is primarily located in the bone marrow. Symptomatic multiple myeloma typically presents with osteolyses, anemia, reduced renal function, and/or hypercalcemia. In the case of such MM-related end organ damage, urgent systemic treatment is indicated. In order to prevent end organ damage, current guidelines now recommend treatment initiation already when certain biomarkers are met. Current first-line treatment is based on proteasome inhibition and immunomodulation...
November 2, 2017: Der Internist
https://www.readbyqxmd.com/read/29095438/baff-is-involved-in-macrophage-induced-bortezomib-resistance-in-myeloma
#10
Jing Chen, Donghua He, Qingxiao Chen, Xing Guo, Li Yang, Xuanru Lin, Yi Li, Wenjun Wu, Yang Yang, Jingsong He, Enfan Zhang, Qing Yi, Zhen Cai
We aimed to characterize the role of B-cell activating factor (BAFF) in macrophage-mediated resistance of multiple myeloma (MM) cells to bortezomib (bort), and to further understand the molecular mechanisms involved in the process. First, we detected BAFF and its three receptors on myeloma cells and macrophages using the quantitative reverse transcriptase-polymerase chain reaction and flow cytometry. The secretion of BAFF was tested in patients with MM, MM cell lines, and macrophages. The ability of macrophages to protect MM cells from bort-induced apoptosis was significantly attenuated using BAFF-neutralizing antibody in the co-culture system or knocking down the expression of BAFF in macrophages with small interfering RNA...
November 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29091798/dna-barcoding-reveals-habitual-clonal-dominance-of-myeloma-plasma-cells-in-the-bone-marrow-microenvironment
#11
Duncan R Hewett, Kate Vandyke, David M Lawrence, Natasha Friend, Jacqueline E Noll, Joel M Geoghegan, Peter I Croucher, Andrew C W Zannettino
Multiple myeloma (MM) is a hematological malignancy resulting from the uncontrolled proliferation of antibody-producing plasma cells in the bone marrow. At diagnosis, independent plasma cell tumors are found throughout the skeleton. The recirculation of mutant plasma cells from the initial lesion and their recolonization of distant marrow sites are thought to occur by a process similar to solid tumor metastasis. However, the efficiency of this bone marrow homing process and the proportion of disseminated cells that actively divide and contribute to new tumor growth in MM are both unknown...
October 26, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29091475/a-review-discussing-elotuzumab-and-its-use-in-the-second-line-plus-treatment-of-multiple-myeloma
#12
Massimo Offidani, Laura Corvatta
Monoclonal antibodies (mAb) represent a new frontier to treat newly diagnosed and relapsed-refractory multiple myeloma (MM). Elotuzumab, an mAb targeted SLAM7 in the plasma cells and natural killer cells surface, is the first mAb approved for the treatment of relapsed-refractory MM in combination with lenalidomide and dexamethasone. This approval was the final result of several preclinical and Phase I-II clinical studies leading to ELOQUENT-2 Phase III trial that demonstrated that elotuzumab adds a significant and durable value to standard therapy, paved the way of this new treatment strategy for MM...
November 1, 2017: Future Oncology
https://www.readbyqxmd.com/read/29089311/slamf7-car-t-cells-eliminate-myeloma-and-confer-selective-fratricide-of-slamf7-normal-lymphocytes
#13
Tea Gogishvili, Sophia Danhof, Sabrina Prommersberger, Julian Rydzek, Martin Schreder, Christian Brede, Hermann Einsele, Michael Hudecek
SLAMF7 is under intense investigation as a target for immunotherapy in multiple myeloma. Here, we redirected the specificity of T-cells to SLAMF7 through expression of a chimeric antigen receptor (CAR) derived from the huLuc63 antibody (Elotuzumab), and demonstrate that SLAMF7-CAR T-cells prepared from patients and healthy donors confer potent antimyeloma reactivity. We confirmed uniform, high-level expression of SLAMF7 on malignant plasma cells in previously untreated and in relapsed/refractory (R/R) myeloma patients who had received prior treatment with proteasome-inhibitors and immunomodulatory agents (IMiDs)...
October 31, 2017: Blood
https://www.readbyqxmd.com/read/29079457/autologous-allogeneic-hematopoietic-cell-transplantation-hct-versus-tandem-autologous-transplantation-for-multiple-myeloma-comparison-of-long-term-post-relapse-survival
#14
Myo Htut, Anita D'Souza, Amrita Krishnan, Benedetto Bruno, Mei-Jie Zhang, Mingwei Fei, Miguel Angel Diaz, Edward Copelan, Siddhartha Ganguly, Mehdi Hamadani, Mohamed Kharfan-Dabaja, Hillard Lazarus, Cindy Lee, Kenneth Meehan, Taiga Nishihori, Ayman Saad, Sachiko Seo, Muthalagu Ramanathan, Saad Z Usmani, Christina Gasparetto, Tomer M Mark, Yago Nieto, Parameswaran Hari
We compared post-relapse overall survival (OS) after autologous-allogenenic (auto/allo) versus tandem autologous (auto/auto) hematopoietic cell transplantation (HCT) in multiple myeloma (MM). Post-relapse survival of patients receiving an auto/auto or auto/allo HCT for MM and prospectively reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) between 2000 and 2010 were analyzed. 404 patients (72.4%) relapsed in the auto/auto group and 178 patients (67.4%) relapsed in the auto/allo group after a median follow up of 8...
October 24, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29076054/prevalence-of-use-and-cost-of-biological-drugs-for-cancer-treatment-a-5-year-picture-from-southern-italy
#15
Simona Lucchesi, Ilaria Marcianò, Paolo Panagia, Rosanna Intelisano, Maria Pia Randazzo, Carmela Sgroi, Giuseppe Altavilla, Mariacarmela Santarpia, Vincenzo Adamo, Tindara Franchina, Francesco Ferraù, Paolina Reitano, Gianluca Trifirò
BACKGROUND AND OBJECTIVES: Considering the clinical and economic burden of biological drugs in cancer treatment, it is necessary to explore how these drugs are used in routine care in Italy and how they affect the sustainability of the National Health Services. This study aimed to investigate the prevalence of use and costs of biological drugs for cancer treatment in a general population of Southern Italy in the years 2010-2014. METHODS: This was a retrospective, observational study using data from the healthcare administrative databases of Messina Province for the years 2010-2014...
October 26, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/29064484/jam-a-as-a-prognostic-factor-and-new-therapeutic-target-in-multiple-myeloma
#16
A G Solimando, A Brandl, K Mattenheimer, C Graf, M Ritz, A Ruckdeschel, T Stühmer, Z Mokhtari, M Rudelius, J Dotterweich, M Bittrich, V Desantis, R Ebert, P Trerotoli, M A Frassanito, A Rosenwald, A Vacca, H Einsele, F Jakob, A Beilhack
Cell adhesion in the multiple myeloma (MM) microenvironment has been recognized as a major mechanism of MM cell survival and the development of drug resistance. Here we addressed the hypothesis that the protein junctional adhesion molecule-A (JAM-A) may represent a novel target and a clinical biomarker in MM. We evaluated JAM-A expression in MM cell lines and in 147 MM patient bone marrow aspirates and biopsies at different disease stages. Elevated JAM-A levels in patient-derived plasma cells were correlated with poor prognosis...
September 28, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29062027/harnessing-a-catalytic-lysine-residue-for-the-one-step-preparation-of-homogeneous-antibody-drug-conjugates
#17
Alex R Nanna, Xiuling Li, Even Walseng, Lee Pedzisa, Rebecca S Goydel, David Hymel, Terrence R Burke, William R Roush, Christoph Rader
Current strategies to produce homogeneous antibody-drug conjugates (ADCs) rely on mutations or inefficient conjugation chemistries. Here we present a strategy to produce site-specific ADCs using a highly reactive natural buried lysine embedded in a dual variable domain (DVD) format. This approach is mutation free and drug conjugation proceeds rapidly at neutral pH in a single step without removing any charges. The conjugation chemistry is highly robust, enabling the use of crude DVD for ADC preparation. In addition, this strategy affords the ability to precisely monitor the efficiency of drug conjugation with a catalytic assay...
October 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/29057477/the-mip-1%C3%AE-autocrine-loop-contributes-to-decreased-sensitivity-to-anticancer-drugs
#18
Masanobu Tsubaki, Tomoya Takeda, Yoshika Tomonari, Kenji Mashimo, Yu-Ichi Koumoto, Sachi Hoshida, Tatsuki Itoh, Motohiro Imano, Takao Satou, Katsuhiko Sakaguchi, Shozo Nishida
Several autocrine soluble factors, including macrophage inflammatory protein-1α (MIP-1α), tumor necrosis factor-α, and hepatocyte growth factor, promote cell survival and growth in multiple myeloma (MM) cells. We hypothesized that inhibition of the MIP-1α autocrine loop may enhance the cytotoxic effect of anticancer drugs in MM cell lines. In the present study, an MIP-1α neutralizing antibody suppressed cell proliferation and enhanced the cytotoxic effect of melphalan or bortezomib on MM cells. In addition, melphalan resistance cells (RPMI8226/L-PAM and HS-sultan/L-PAM cells) secreted MIP-1α and neutralizing antibody of MIP-1α partially overcame melphalan resistance...
October 23, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29054515/blood-transfusion-management-and-transfusion-related-outcomes-in-daratumumab-treated-patients-with-relapsed-or-refractory-multiple-myeloma
#19
Ajai Chari, Suzanne Arinsburg, Sundar Jagannath, Toshihisa Satta, Ivey Treadwell, Donna Catamero, Gillian Morgan, Huaibao Feng, Clarissa Uhlar, Imran Khan, Parul Doshi, Saad Usmani
INTRODUCTION: Daratumumab, a human CD38 monoclonal antibody approved for multiple myeloma (MM) treatment, binds red blood cells (RBCs), resulting in panagglutination in compatibility tests. Published mitigation methods avoid additional testing, ensuring timely release of blood products. Blood transfusion management and transfusion-related outcomes of daratumumab-treated patients in the SIRIUS study are reported, with emphasis on 2 clinical sites. PATIENTS AND METHODS: Patients had MM treated with ≥ 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug, or were refractory to a proteasome inhibitor and an immunomodulatory drug...
September 19, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29053503/lenalidomide-associated-thyroid-related-eyelid-retraction
#20
Geraldine R Slean, Rona Z Silkiss
Several antineoplastic treatments have been responsible for thyroid dysfunction and thyroid eye disease. Min, Vaidya, and Becker (2011) reported a case of euthyroid Graves orbitopathy after treatment with ipilimumab with the patient displaying proptosis and myositis in the setting of normal thyroid function tests and elevated thyroid antibodies. The authors report a case of a 76-year-old woman who developed right upper lid retraction and proptosis after 2.5 years of treatment with lenalidomide for multiple myeloma...
October 19, 2017: Ophthalmic Plastic and Reconstructive Surgery
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