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Krista Kinneer, Matt Flynn, Suneetha B Thomas, John Meekin, Reena Varkey, Xiaodong Xiao, Haihong Zhong, Shannon Breen, Paul G Hynes, Ryan Fleming, Binyam Bezabeh, Cui Tracy Chen, Leslie Wetzel, Ruoyan Chen, Nazzareno Dimasi, Yu-Tzu Tai, Kenneth C Anderson, Ronald Herbst, Philip W Howard, Elaine M Hurt, David A Tice
No abstract text is available yet for this article.
October 12, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Hideto Tamura
Multiple myeloma (MM) involves the immune dysregulation not only of B cells but also of NK, T, and dendritic cells. Furthermore, the number of regulatory T and myeloid-derived immunosuppressive cells, which are associated with disease progression, also increases. Immunomodulatory drugs (IMiDs) such as lenalidomide and pomalidomide exhibit an antimyeloma effect and improve the immune status. Thus, IMiD-enhanced antibody-dependent cell cytotoxicity increases the cytotoxic activity of monoclonal antibody treatment...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Zoe Shancer, Matthew Williams, Austin Igelman, Satoshi Nagata, Tomoko Ise, Ira Pastan, Tapan K Bera
Background: Multiple myeloma (MM) is a B-cell malignancy that is incurable for the majority of patients. New treatments are urgently needed. Recombinant immunotoxins (RITs) are chimeric proteins that are composed of the Fv or Fab portion of an antibody fused to a bacterial toxin. B-cell maturation antigen (BCMA) is a lineage-restricted differentiation protein and an ideal target for antibody-based treatments for MM. Methods: RITs were produced by expressing plasmids encoding the components of the anti-BCMA RITs in Escherichia coli followed by inclusion body preparation, solubilization, renaturation, and purification by column chromatography...
June 2018: Antibody therapeutics
Adam D Cohen
Cellular therapies are a rapidly evolving approach to myeloma treatment, which bring a unique mechanism of action with the potential to overcome drug resistance and induce long-term remissions. Two primary approaches are being studied: non-gene-modified strategies, which rely on the endogenous anti-myeloma T-cell repertoire, and gene-modified strategies, which introduce a new T-cell receptor (TCR) or a chimeric antigen receptor (CAR) to confer novel antigen specificity. CAR T cells show the greatest activity to date...
May 23, 2018: American Society of Clinical Oncology Educational Book
Robert Berahovich, Hua Zhou, Shirley Xu, Yuehua Wei, Jasper Guan, Jian Guan, Hizkia Harto, Shuxiang Fu, Kaihuai Yang, Shuying Zhu, Le Li, Lijun Wu, Vita Golubovskaya
The cell-surface protein B cell maturation antigen (BCMA, CD269) has emerged as a promising target for CAR-T cell therapy for multiple myeloma. In order to create a novel BCMA CAR, we generated a new BCMA monoclonal antibody, clone 4C8A. This antibody exhibited strong and selective binding to human BCMA. BCMA CAR-T cells containing the 4C8A scFv were readily detected with recombinant BCMA protein by flow cytometry. The cells were cytolytic for RPMI8226, H929, and MM1S multiple myeloma cells and secreted high levels of IFN-γ in vitro...
September 11, 2018: Cancers
Ken Ohmine
A chimeric antigen receptor (CAR) comprises an extracellular ligand recognition domain linked to CD3ζ and induces T-cell activation upon antigen binding. Recently, the potential of CD19-targeted CAR T-cells (CAR-T) to treat multiple myeloma has been explored. A group in the University of Pennsylvania reported that 4 out of 10 patients with refractory myeloma achieved an objective response (sCR: 1, VGPR: 1, and PR: 2). Although the resultant cancer ablation was an arresting sight, it remains unclear whether CD19 is a suitable target for myeloma...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Lorena Perez-Amill, Berta Marzal, Alvaro Urbano-Ispizua, Manel Juan, Beatriz Martín-Antonio
Seven years ago a chronic lymphocytic leukemia patient was by first time successfully treated with chimeric antigen receptor (CAR)-modified T cells (CART cells) to target CD19 over-expressed in tumor cells. This was the beginning of the development for a new type of immunotherapy treatment in cancer patients. Since then, identification of novel antigens expressed in the tumor cell, and optimization of both CARs constructs and protocols of administration have opened up new avenues to be able to treat successfully other hematological malignancies...
September 6, 2018: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
Shih-Feng Cho, Kenneth C Anderson, Yu-Tzu Tai
The approval of the first two monoclonal antibodies targeting CD38 (daratumumab) and SLAMF7 (elotuzumab) in late 2015 for treating relapsed and refractory multiple myeloma (RRMM) was a critical advance for immunotherapies for multiple myeloma (MM). Importantly, the outcome of patients continues to improve with the incorporation of this new class of agents with current MM therapies. However, both antigens are also expressed on other normal tissues including hematopoietic lineages and immune effector cells, which may limit their long-term clinical use...
2018: Frontiers in Immunology
Vasiliki Pelekanou, George Notas, Paraskevi Athanasouli, Konstantinos Alexakis, Fotini Kiagiadaki, Nikolaos Peroulis, Konstantina Kalyvianaki, Errika Kampouri, Hara Polioudaki, Panayiotis Theodoropoulos, Andreas Tsapis, Elias Castanas, Marilena Kampa
Recent advances in cancer immunology revealed immune-related properties of cancer cells as novel promising therapeutic targets. The two TNF superfamily members, APRIL (TNFSF13), and BAFF (TNFSF13B), which are type II membrane proteins, released in active forms by proteolytic cleavage and are primarily involved in B-lymphocyte maturation, have also been associated with tumor growth and aggressiveness in several solid tumors, including breast cancer. In the present work we studied the effect of APRIL and BAFF on epithelial to mesenchymal transition, migration, and stemness of breast cancer cells...
2018: Frontiers in Oncology
Krista Kinneer, John Meekin, Arnaud C Tiberghien, Yu-Tzu Tai, Sandrina Phipps, Christine Mione Kiefer, Marlon C Rebelatto, Nazzareno Dimasi, Alyssa D Moriarty, Kyriakos P Papadopoulos, Sriram Sridhar, Stephen J Gregson, Michael J Wick, Luke A Masterson, Kenneth C Anderson, Ronald Herbst, Philip W Howard, David A Tice
PURPOSE: Antibody-drug conjugates (ADCs) utilizing non-cleavable linker-drugs have been approved for clinical use, and several are in development targeting solid and hematological malignancies including multiple myeloma (MM). Currently there are no reliable biomarkers of activity for these ADCs other than presence of the targeted antigen. We observed that certain cell lines are innately resistant to such ADCs, and sought to uncover the underlying mechanism of resistance. EXPERIMENTAL DESIGN: The expression of 43 lysosomal membrane target genes was evaluated in cell lines resistant to ADCs bearing the non-cleavable linker pyrrolobenzodiazepine payload SG3376 in vitro...
August 21, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Julia Bluhm, Elisa Kieback, Stephen F Marino, Felix Oden, Jörg Westermann, Markus Chmielewski, Hinrich Abken, Wolfgang Uckert, Uta E Höpken, Armin Rehm
Autologous T cells genetically modified with a chimeric antigen receptor (CAR) redirected at CD19 have potent activity in the treatment of B cell leukemia and B cell non-Hodgkin's lymphoma (B-NHL). Immunotherapies to treat multiple myeloma (MM) targeted the B cell maturation antigen (BCMA), which is expressed in most cases of MM. We developed a humanized CAR with specificity for BCMA based on our previously generated anti-BCMA monoclonal antibody. The targeting single-chain variable fragment (scFv) domain exhibited a binding affinity in the low nanomolar range, conferring T cells with high functional avidity...
August 1, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Edgar Meinl, Franziska S Thaler, Stefan F Lichtenthaler
Proteolytic shedding of the receptors BCMA, TACI, and BAFFR reduces their cell-surface expression and ligand-mediated survival of B cell subsets. This shedding is executed by protease γ-secretase or by metalloproteases, and is partially dependent on ligand binding and receptor interactions. Shed receptors may serve as biomarkers for autoimmunity and lymphoma.
September 2018: Trends in Immunology
Dalia A Salem, Irina Maric, Constance M Yuan, David J Liewehr, David J Venzon, James Kochenderfer, Maryalice Stetler-Stevenson
B-cell maturation antigen (BCMA) is expressed by normal and malignant plasma cells and is targeted via anti-BCMA chimeric antigen receptor T-cell therapy (BCMA CAR T-cell therapy) in plasma cell myeloma (PCM) patients. Surface BCMA expression is required for CAR T-cell binding and killing. We determined the incidence and intensity of expression of BCMA in bone marrow PCM cells using flow cytometry (FC) and immunohistochemistry (IHC). PCM BCMA expression was assessed by FC in 70 patients and in 43 concurrent specimens by IHC...
August 2018: Leukemia Research
Sophia Danhof, Michael Hudecek, Eric L Smith
Harnessing the endogenous immune system to eliminate malignant cells has long been an intriguing approach. After considerable success in the treatment of B-cell acute lymphoblastic leukemia, chimeric antigen receptor (CAR)-modified T cells have entered early clinical evaluation in the field of multiple myeloma (MM). The choice of suitable non-CD19 target antigens is challenging and a variety of myeloma-associated surface molecules have been under preclinical investigation. Most recent clinical protocols have focused on targeting B-cell maturation antigen (BCMA), and early results are promising...
June 2018: Best Practice & Research. Clinical Haematology
Hao Xu, Wenyue Cao, Liang Huang, Min Xiao, Yang Cao, Lei Zhao, Na Wang, Jianfeng Zhou
Chimeric antigen receptor T (CART) cell therapy has emerged as a potentially curative "drug" for cancer treatment. Cryopreservation of CART cells is necessary for their clinical application. Systematic studies on the effects of cryopreservation on the antitumor function of CART cells are lacking. Therefore, we compared the phenotypes and functions of CART cells that were cryopreserved during ex vivo expansion with those of freshly isolated populations. T cells expressing an anti-B-cell-maturation-antigen (BCMA) chimeric antigen receptor (CAR) were expanded in vitro for 10 days and then cryopreserved...
August 2018: Cryobiology
De-Xiu Bu, Reshma Singh, Eugene E Choi, Marco Ruella, Selene Nunez-Cruz, Keith G Mansfield, Paul Bennett, Nathanial Barton, Qilong Wu, Jiquan Zhang, Yongqiang Wang, Lai Wei, Shawn Cogan, Tucker Ezell, Shree Joshi, Kellie J Latimer, Brian Granda, William R Tschantz, Regina M Young, Heather A Huet, Celeste J Richardson, Michael C Milone
Multiple myeloma has a continued need for more effective and durable therapies. B cell maturation antigen (BCMA), a plasma cell surface antigen and member of the tumor necrosis factor (TNF) receptor superfamily, is an attractive target for immunotherapy of multiple myeloma due to its high prevalence on malignant plasma cells. The current work details the pre-clinical evaluation of BCMA expression and development of a chimeric antigen receptor (CAR) targeting this antigen using a fully human single chain variable fragment (scFv)...
May 25, 2018: Oncotarget
Ichiro Hanamura, Shinsuke Iida
Proteasome inhibitors and immunomodulatory drugs have substantially improved the clinical outcomes in patients with multiple myeloma (MM) since 2000. In 2015, the new monoclonal antibodies, daratumumab and elotuzumab, were approved for treating relapsed and/or refractory MM (RRMM). Furthermore, venetoclax, a selective BCL-2 inhibitor, and chimeric antigen receptor (CAR) T-cell therapy that work against B-cell maturation antigen (BCMA) have reportedly shown great efficacy in phase 1 studies. The efficacy of venetoclax has been observed in RRMM with t (11;14) and higher BCL-2/BCL-XL expression...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Liliana Giraldo, Bibiana Schachner, Daniel Luna, Sonia Benítez
The inclusion of new technologies in health, such as the 2D Codes scanning Drug Administration System (BCMA), has an impact on the perception of nurses, mainly changes in their workflow, and incorporation of mobile devices for patient care. The objective of this study is to know the perceptions and expectations of nurses regarding the implementation of BCMA. Qualitative research was conducted based on interviews with groups of nurses from different inpatient wards of the Hospital Italiano de Buenos Aires, with and without system implementation...
2018: Studies in Health Technology and Informatics
Jennifer N Brudno, Irina Maric, Steven D Hartman, Jeremy J Rose, Michael Wang, Norris Lam, Maryalice Stetler-Stevenson, Dalia Salem, Constance Yuan, Steven Pavletic, Jennifer A Kanakry, Syed Abbas Ali, Lekha Mikkilineni, Steven A Feldman, David F Stroncek, Brenna G Hansen, Judith Lawrence, Rashmika Patel, Frances Hakim, Ronald E Gress, James N Kochenderfer
Purpose Therapies with novel mechanisms of action are needed for multiple myeloma (MM). T cells can be genetically modified to express chimeric antigen receptors (CARs), which are artificial proteins that target T cells to antigens. B-cell maturation antigen (BCMA) is expressed by normal and malignant plasma cells but not normal essential cells. We conducted the first-in-humans clinical trial, to our knowledge, of T cells expressing a CAR targeting BCMA (CAR-BCMA). Patients and Methods Sixteen patients received 9 × 106 CAR-BCMA T cells/kg at the highest dose level of the trial; we are reporting results of these 16 patients...
August 1, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Abbas Sheikhtaheri, Samane Saravani-Aval
Medication errors are common in healthcare settings. To prevent these errors, use of modern technology is suggested. Improvement of medication administration system particularly at the time of drug administration is mandated in Iran. Barcode medication administration (BCMA) systems are useful in this regard. This study was conducted to assess nurses' attitude for the use of BCMA systems. To this end, 283 randomly selected nurses working in teaching hospitals were surveyed using a five point Likert scale questionnaire...
2018: Studies in Health Technology and Informatics
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