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Takayuki Yamamoto, Qi Li, Hidetaka Hara, Liaoran Wang, Hongmin Zhou, Juan Li, Devin E Eckhoff, A Joseph Tector, Edwin C Klein, Ray Lovingood, Mohamed Ezzelarab, David Ayares, Yi Wang, David K C Cooper, Hayato Iwase
BACKGROUND: In the pig-to-baboon artery patch model with no immunosuppressive therapy, a graft from an α1,3-galactosyltransferase gene-knockout (GTKO) pig elicits a significant anti-nonGal IgG response, indicating sensitization to the graft. A costimulation blockade-based regimen, e.g., anti-CD154mAb or anti-CD40mAb, prevents sensitization. However, neither of these agents is currently FDA-approved. The aim of the present study was to determine the efficacy of FDA-approved agents on the T and B cell responses...
August 6, 2018: Transplant Immunology
Zaina T Al-Salama
The intravenous CD22-directed antibody drug conjugate inotuzumab ozogamicin (Besponsa® ) is approved in several countries including in the USA, EU and Japan, as monotherapy for the treatment of adults with relapsed/refractory B-cell acute lymphoblastic leukaemia (ALL). In adults with relapsed/refractory B-cell ALL who had received one or two prior treatment regimens, inotuzumab ozogamicin was associated with significantly higher rates of complete remission (including complete remission with incomplete haematological recovery) [CR/CRi] than standard therapy in the pivotal INO-VATE ALL trial...
August 9, 2018: Targeted Oncology
Dilip K Das
Some of the limitations of fine needle aspiration (FNA) in the cytodiagnosis of lymphoma include problems encountered in differentiating reactive hyperplasia from low-grade non-Hodgkin lymphoma (NHL), lower cytodiagnostic accuracy for NHL with a follicular (nodular) pattern and nodular sclerosis type of classical Hodgkin lymphoma (HL), and overlapping morphological features between T-cell-rich B-cell lymphoma (TCRBCL), anaplastic large cell lymphoma (ALCL), and HL. Immunocytochemistry may be of help in such situations...
July 2018: Journal of Cytology
Ilana R Yurkiewicz, Lori Muffly, Michaela Liedtke
Despite improved rates of remission and cure in newly diagnosed adult acute lymphoblastic leukemia (ALL), the prognosis for patients with relapsed or refractory disease remains poor and the 5-year overall survival rate after relapse is under 10%. A recent paradigm shift has focused on the promise of targeted immunotherapy rather than standard chemotherapy, as ALL blast cells express a variety of antigens, and monoclonal antibodies may be developed to identify and destroy the leukemic cells. Inotuzumab ozogamicin is a CD22 monoclonal antibody conjugated to the cytotoxic antibiotic calicheamicin...
2018: Drug Design, Development and Therapy
Hubert Lau, Alexandra Nagy, Susan K Atwater, Michael J Cascio, Robert S Ohgami
INTRODUCTION: CD13 is a myeloid associated antigen, which may be expressed by a subset of B cell lymphomas; however, the significance of its expression along with other B cell associated antigens is not well characterized. METHODS: Two hundred and eighty-six mature B cell neoplasms with flow cytometric analysis performed at the time of diagnosis were identified. Expression of CD13, CD45, CD19, CD20, CD5, CD10, CD38, CD22, CD23, FMC7, and kappa and lambda light chains was assessed for each case and correlated with clinicopathologic features...
July 31, 2018: International Journal of Laboratory Hematology
Haneen Shalabi, Pamela L Wolters, Staci Martin, Mary Anne Toledo-Tamula, Marie Claire Roderick, Kari Struemph, Eli Kane, Bonnie Yates, Cindy Delbrook, Crystal L Mackall, Daniel W Lee, Terry J Fry, Nirali N Shah
Neurotoxicity associated with CAR-T cell therapy can be life-threatening. With rapid development of CAR-T therapies, a systematic method is needed to identify and monitor symptoms of neurotoxicity, elucidate potential etiologies, and compare toxicity across trials. This paper presents a systematic evaluation developed and used to prospectively assess neurotoxicity in our phase I anti-CD22 CAR-T-cell trial and describes the symptoms of neurotoxicity identified using this methodology. Central nervous system (CNS) studies included routine lumbar punctures performed for disease evaluation pretherapy and posttherapy and a baseline brain MRI...
September 2018: Journal of Immunotherapy
June Ereño-Orbea, Taylor Sicard, Hong Cui, Indira Akula, Jean-Philippe Julien
Glycoproteins on the surface of cells play critical roles in cellular function, including signalling, adhesion and transport. On leukocytes, several of these glycoproteins possess immunoglobulin (Ig) folds and are central to immune recognition and regulation. Here, we present a platform for the design, expression and biophysical characterization of the extracellular domain of human B cell receptor CD22. We propose that these approaches are broadly applicable to the characterization of mammalian glycoprotein ectodomains containing Ig domains...
July 5, 2018: Journal of Visualized Experiments: JoVE
A Daschuk, Ye Dobrzhanskaya, N Pustovaya
The purpose of the study was to follow the casual mechanism of exacerbation, progression and formation of severe forms of psoriasis, as well as the progression of cutaneous manifestation of psoriasis with the definition of the role of stress response in their development by analyzing features of the psoriasis dynamics on the example of reviewing clinical case in anamnesis. MATERIALS AND METHODS: Examination of the psychosomatic condition and stress-making immunoneuroendocrine system of the patient with psoriasis was conducted at the beginning of disease and in the remission period of psoriasis...
June 2018: Georgian Medical News
Robert J Kreitman, Claire Dearden, Pier Luigi Zinzani, Julio Delgado, Lionel Karlin, Tadeusz Robak, Douglas E Gladstone, Philipp le Coutre, Sascha Dietrich, Mirjana Gotic, Loree Larratt, Fritz Offner, Gary Schiller, Ronan Swords, Larry Bacon, Monica Bocchia, Krimo Bouabdallah, Dimitri A Breems, Agostino Cortelezzi, Shira Dinner, Michael Doubek, Bjorn Tore Gjertsen, Marco Gobbi, Andrzej Hellmann, Stephane Lepretre, Frederic Maloisel, Farhad Ravandi, Philippe Rousselot, Mathias Rummel, Tanya Siddiqi, Tamar Tadmor, Xavier Troussard, Cecilia Arana Yi, Giuseppe Saglio, Gail J Roboz, Kemal Balic, Nathan Standifer, Peng He, Shannon Marshall, Wyndham Wilson, Ira Pastan, Nai-Shun Yao, Francis Giles
This is a pivotal, multicenter, open-label study of moxetumomab pasudotox, a recombinant CD22-targeting immunotoxin, in hairy cell leukemia (HCL), a rare B cell malignancy with high CD22 expression. The study enrolled patients with relapsed/refractory HCL who had ≥2 prior systemic therapies, including ≥1 purine nucleoside analog. Patients received moxetumomab pasudotox 40 µg/kg intravenously on days 1, 3, and 5 every 28 days for ≤6 cycles. Blinded independent central review determined disease response and minimal residual disease (MRD) status...
July 20, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Behzad Poopak, Adnan Khosravi, Gholamreza Bahoush-Mehdiabadi, Tahereh Madani, Elahe Khodadi, Zohreh Farahani, Amir Ali Vahedi, Gelareh Khosravipour, Peyvand Poopak, Amir Hossein Poopak
Mixed-phenotype acute leukemia (MPAL) is the infrequent type of acute leukemia characterized by immunophenotypic and/or cytochemical features of both lineages, but the diagnosis of this disease still is a challenge. In this study, we analyzed immunophenotyping, cytochemistry and frequency of MPAL patients to better diagnosis of MPAL characteristics according to WHO 2016 criteria for the first time in Iran. In this retrospective study, 27 patients were diagnosed as MPAL based on WHO 2016 criteria during 2014-2017...
July 17, 2018: Clinical and Experimental Medicine
Tyler A Herek, Jacob E Robinson, Tayla B Heavican, Catalina Amador, Javeed Iqbal, Christine E Cutucache
OBJECTIVE: Caveolin-1 (CAV1) is known for its role as both a tumor suppressor and an oncogene, harboring a highly context-dependent role within a myriad of malignancies and cell types. In an immunological context, dysregulation of CAV1 expression has been shown to alter immunological signaling functions and suggests a pivotal role for CAV1 in the facilitation of proper immune responses. Nonetheless, it is still unknown how Cav1-deficiency and heterozygosity would impact the development and composition of lymphoid organs in mice...
July 13, 2018: BMC Research Notes
Amy Starr, Dong Hyang Kwon, Bhaskar Kallakury
Diffuse large B-cell lymphoma (DLBCL) is characterized by medium- to large-sized neoplastic cells that express a wide range of B-cell markers including CD19, CD20, CD22, and CD79a. Also, as this is a hematopoietic malignancy, there is expression of the leukocyte common antigen CD45. Lack of CD20 expression occurs in a specific rare heterogeneous subgroup of DLBCL including primary effusion lymphoma, plasmablastic lymphoma, ALK-positive large B-cell lymphoma, and large B-cell lymphoma arising in HHV8+ multicentric Castleman disease...
June 1, 2018: International Journal of Surgical Pathology
Elias Jabbour, Ching-Hon Pui, Hagop Kantarjian
Importance: Remarkable progress has occurred in understanding the pathophysiology and in developing improved personalized therapies in adult acute lymphoblastic leukemia (ALL). Observations: We searched MEDLINE (1990-2018), the American Society of Clinical Oncology, and American Society of Hematology websites (2010-2018). We used the search terms "acute lymphoblastic or lymphocytic leukemia" or "ALL." We largely selected publications in the past 5 years but did not exclude commonly referenced and highly regarded older publications...
June 21, 2018: JAMA Oncology
Seyed Reza Banihashemi, Ahmad Zavaran Hosseini, Fatemeh Rahbarizadeh, Davoud Ahmadvand
Objectives: CD19 is a transmembrane glycoprotein of immunoglobulin superfamily. In order to treat lymphoma, monoclonal antibodies (mAb) can target different antigens, including CD19, CD20 and CD22 on the surface of B-cells. Along with biotechnology progress, a new generation of antibodies is introduced, with the purpose of eliminating the defects of the previous generation. Among the most developed one are nanobodies (Nb). Nbs are a unique kind of camelid single domain antibody fragments with a broad range of medical applications...
May 2018: Iranian Journal of Basic Medical Sciences
Meijiao Zhang, Shizhu Zang, Guangbo Ge, Lingling Jin, Yi Xin, Huizhen Li, Pingkun Liu, Xudong Hou, Dacheng Hao, Lu Chen, Qi Zhou, Jie Hou
CD22 is an important drug target for the treatment of autoimmune diseases and B cell-derived malignancies. In this study, N-acetylneuraminic acid functionalized quantum dots nanoconjugate was synthesized and used for targeting and fluorescence imaging of CD22 on living cells. The nanoprobe was prepared by conjugating N-acetylneuraminic acid (NANA) on the carboxyl groups modified CdSe/ZnS quantum dots (COOH-QDs) via NHS/EDC mediated esterification. The NANA-QDs nanoprobe showed excellent size distribution, very low cytotoxicity and super fluorescent properties for biological imaging applications...
August 1, 2018: Journal of Biomedical Nanotechnology
Fabian Müller, Tyler Cunningham, Richard Beers, Tapan K Bera, Alan S Wayne, Ira Pastan
Moxetumomab pasudotox is a fusion protein of a CD22-targeting antibody and Pseudomonas exotoxin. Minutes of exposure to Moxetumomab achieves similar cell killing than hours of exposure to a novel deimmunized variant against some acute lymphoblastic leukemia (ALL). Because blood levels fall quickly, Moxetumomab is more than 1000-fold more active than the deimmunized variant in vivo. We aimed to identify which part of Moxetumomab increases in vivo efficacy and generated five immunotoxins, tested time-dependent activity, and determined the efficacy in a KOPN-8 xenograft model...
May 21, 2018: Toxins
Konstantinos Melissaropoulos, Stamatis-Nick Liossis
The objective of the study was to explore the phenotype and intracellular signaling events of B cells in patients with systemic sclerosis (SSc). Peripheral blood B cell surface markers CD19 and CD22 were evaluated by flow cytometry in 23 patients with SSc and seven healthy individuals. Levels of intracellular kinases Lyn, Syk and P-Y 348 Syk along with phosphatase SHP-1 were examined with Western immunoblotting in selected patients. P-Y 822 CD22 was subsequently evaluated flow cytometrically in antigen receptor stimulated B cells...
July 2018: Rheumatology International
Katharina Blatt, Ingeborg Menzl, Gregor Eisenwort, Sabine Cerny-Reiterer, Harald Herrmann, Susanne Herndlhofer, Gabriele Stefanzl, Irina Sadovnik, Daniela Berger, Alexandra Keller, Alexander Hauswirth, Gregor Hoermann, Michael Willmann, Thomas Rülicke, Heinz Sill, Wolfgang R Sperr, Christine Mannhalter, Junia V Melo, Ulrich Jäger, Veronika Sexl, Peter Valent
Leukemic stem cells (LSCs) are an emerging target of curative anti-leukemia therapy. In acute lymphoblastic leukemia (ALL), LSCs frequently express CD34 and often lack CD38. However, little is known about markers and targets expressed in ALL LSCs. We have examined marker- and target expression profiles in CD34+ /CD38- LSCs in patients with Ph+ ALL (n = 22) and Ph- ALL (n = 27) by multi-color flow cytometry and qPCR. ALL LSCs expressed CD19 (B4), CD44 (Pgp-1), CD123 (IL-3RA), and CD184 (CXCR4) in all patients tested...
June 2018: Neoplasia: An International Journal for Oncology Research
Bálint Egyed, Gábor Kovács, Nóra Kutszegi, Andrea Rzepiel, Judit Csányiné Sági, Dániel János Erdélyi, Judit Müller, Ágnes Félné Semsei
Owing to clinical trials and improvement over the past few decades, the majority of children with acute lymphoblastic leukemia (ALL) survive by first-line chemotherapy and combat with the problems of returning to community. However, many patients may have severe acute or late therapeutic side effects, and the survival rate in some groups (e.g., patients with MLL rearrangements, hypodiploidy, IKZF1 mutation or early precursor T cell phenotype) is far behind the average. Innovative strategies in medical attendance provide better clinical outcomes for them: complete gene diagnostics, molecularly targeted anticancer treatment, immuno-oncology and immune cell therapy...
May 2018: Orvosi Hetilap
Kim F Bornhöfft, Tom Goldammer, Alexander Rebl, Sebastian P Galuska
Siglecs (sialic acid-binding immunoglobulin-type lectins) are a family of immune regulatory receptors predominantly found on the cells of the hematopoietic system. A V-set Ig-like domain mediates the recognition of different sialylated glycoconjugates, which can lead to the activation or inhibition of the immune response, depending on the involved Siglecs. Siglecs are categorized into two subgroups: one including all CD33-related Siglecs and the other consisting of Siglec-1 (Sialoadhesin), Siglec-2 (CD22), Siglec-4 (myelin-associated glycoprotein, MAG) and Siglec-15...
September 2018: Developmental and Comparative Immunology
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