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https://www.readbyqxmd.com/read/29679060/mechanically-interlocked-functionalization-of-monoclonal-antibodies
#1
Krzysztof P Bzymek, James W Puckett, Cindy Zer, Jun Xie, Yuelong Ma, Jeremy D King, Leah H Goodstein, Kendra N Avery, David Colcher, Gagandeep Singh, David A Horne, John C Williams
Because monoclonal antibodies (mAbs) have exceptional specificity and favorable pharmacology, substantial efforts have been made to functionalize them, either with potent cytotoxins, biologics, radionuclides, or fluorescent groups for therapeutic benefit and/or use as theranostic agents. To exploit our recently discovered meditope-Fab interaction as an alternative means to efficiently functionalize mAbs, we used insights from the structure to enhance the affinity and lifetime of the interaction by four orders of magnitude...
April 20, 2018: Nature Communications
https://www.readbyqxmd.com/read/29678836/tumor-suppressor-bap1-is-essential-for-thymic-development-and-proliferative-responses-of-t-lymphocytes
#2
Teresita L Arenzana, Steve Lianoglou, Akiko Seki, Celine Eidenschenk, Tommy Cheung, Dhaya Seshasayee, Thijs Hagenbeek, Arivazhagan Sambandam, Rajkumar Noubade, Ivan Peng, Justin Lesch, Jason DeVoss, Xiumin Wu, Wyne P Lee, Patrick Caplazi, Joshua Webster, Jinfeng Liu, Victoria C Pham, David Arnott, Jennie R Lill, Zora Modrusan, Anwesha Dey, Sascha Rutz
Loss of function of the nuclear deubiquitinating enzyme BRCA1-associated protein-1 (BAP1) is associated with a wide spectrum of cancers. We report that tamoxifen-induced BAP1 deletion in adult mice resulted in severe thymic atrophy. BAP1 was critical for T cell development at several stages. In the thymus, BAP1 was required for progression through the pre-T cell receptor checkpoint. Peripheral T cells lacking BAP1 demonstrated a defect in homeostatic and antigen-driven expansion. Deletion of BAP1 resulted in suppression of E2F target genes and defects in cell cycle progression, which was dependent on the catalytic activity of BAP1, but did not require its interaction with host cell factor-1 (HCF-1)...
April 20, 2018: Science Immunology
https://www.readbyqxmd.com/read/29678657/development-and-evaluation-of-an-optimal-human-single-chain-variable-fragment-derived-bcma-targeted-car-t-cell-vector
#3
Eric L Smith, Mette Staehr, Reed Masakayan, Ishan J Tatake, Terence J Purdon, Xiuyan Wang, Pei Wang, Hong Liu, Yiyang Xu, Sarah C Garrett-Thomson, Steven C Almo, Isabelle Riviere, Cheng Liu, Renier J Brentjens
B cell maturation antigen (BCMA) has recently been identified as an important multiple myeloma (MM)-specific target for chimeric antigen receptor (CAR) T cell therapy. In CAR T cell therapy targeting CD19 for lymphoma, host immune anti-murine CAR responses limited the efficacy of repeat dosing and possibly long-term persistence. This clinically relevant concern can be addressed by generating a CAR incorporating a human single-chain variable fragment (scFv). We screened a human B cell-derived scFv phage display library and identified a panel of BCMA-specific clones from which human CARs were engineered...
March 28, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29678553/recipient-and-donor-cells-in-the-graft-versus-solid-tumor-effect-it-takes-two-to-tango
#4
REVIEW
Isabelle Dierckx de Casterlé, An D Billiau, Ben Sprangers
Allogeneic hematopoietic stem cell transplantation (alloHSCT) produces -similar to the long-established graft-versus-leukemia effect- graft-versus-solid-tumor effects. Clinical trials reported response rates of up to 53%, occurring mostly but not invariably in association with full donor chimerism and/or graft-versus-host disease. Although donor-derived T cells are considered the principal effectors of anti-tumor immunity after alloHSCT or donor leukocyte infusion (DLI), growing evidence indicate that recipient-derived immune cells may also contribute...
April 12, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29678518/pattern-recognition-receptors-mediate-pro-inflammatory-effects-of-extracellular-mitochondrial-transcription-factor-a-tfam
#5
Stephanie M Schindler, Matthew G Frank, Jessica L Annis, Steven F Maier, Andis Klegeris
Neuroinflammation is a common pathogenic mechanism for a number of neurodegenerative disorders including Alzheimer's and Parkinson's diseases. Microglia, the immune cells of the brain, contribute to the onset and progression of the neuroinflammation observed in these diseases. Microglia become activated and initiate an inflammatory response by interacting with a diverse set of molecules, including the group of endogenous proteins released upon cell damage, termed damage-associated molecular patterns (DAMPs)...
April 17, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29678441/acute-lymphoblastic-leukemia-lymphoma-of-the-oral-and-maxillofacial-region
#6
Celeste Sánchez-Romero, Hélder Antônio Rebelo Pontes, Flávia Sirotheau Corrêa Pontes, André Caroli Rocha, Román Carlos, Javier C Rendón, Oslei Paes de Almeida, Felipe Paiva Fonseca
OBJECTIVE: Our objective was to describe the clinicopathologic and immunohistochemical features of acute lymphoblastic leukemia/lymphoma (ALL/LBL) of the oral and maxillofacial region (OMF). STUDY DESIGN: Cases diagnosed as ALL/LBL of the OMF region were retrieved from the files of 2 Brazilian and 1 Guatemalan oral pathology services from 2005 to 2017. Microscopic and immunohistochemical features of each case were reviewed and fully described, and clinical data were retrieved from the pathology reports...
January 31, 2018: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
https://www.readbyqxmd.com/read/29676233/chimeric-antigen-receptor-t-cell-based-immunotherapy-for-cancer
#7
Feng Li, Tengfei Zhang, Ling Cao, Yi Zhang
Cancer immunotherapy, a new weapon against cancers by harnessing the patient's own immune system, potentiates an extended remission and possibly a cure for cancer. T cells genetically engineered with chimeric antigen receptor (CAR) vectors can specifically target the surface antigen of cancer cells and kill them in an MHC-independent manner. CD19 is extensively expressed on cancerous cells in B cell malignancies. To target this antigen, CAR T cells have gained great success in treating patients with B cell leukemia and lymphoma...
April 19, 2018: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29675931/efficacy-studies-of-sclerotium-rolfsii-lectin-on-breast-cancer-using-nod-scid-mouse-model
#8
Prajna Hegde, Jagadeesh Narasimhappagari, Bale M Swamy, Shashikala R Inamdar
Expression of altered glycans like TF, Tn and sTn antigens has been observed in a number of carcinomas which are targeted in cancer therapy. Sclerotium rolfsii lectin (SRL) is known to recognize TF and its substituted forms. Clinical potential of SRL has been demonstrated by studying its interaction with different types of cancer cells. Here we report, in vitro studies of SRL on breast cancer MDA-MB-468 cells and in vivo studies with MCF-7 xenografts. In vitro growth inhibitory studies of SRL on metastatic triple negative breast cancer MDA-MB-468 cells was performed by MTT assay, flow cytometry, adhesion and CAM assay...
April 20, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29675465/elimination-of-established-tumors-with-nanodisc-based-combination-chemoimmunotherapy
#9
Rui Kuai, Wenmin Yuan, Sejin Son, Jutaek Nam, Yao Xu, Yuchen Fan, Anna Schwendeman, James J Moon
Although immune checkpoint blockade has shown initial success for various cancers, only a small subset of patients benefits from this therapy. Some chemotherapeutic drugs have been reported to induce antitumor T cell responses, prompting a number of clinical trials on combination chemoimmunotherapy. However, how to achieve potent immune activation with traditional chemotherapeutics in a manner that is safe, effective, and compatible with immunotherapy remains unclear. We show that high-density lipoprotein-mimicking nanodiscs loaded with doxorubicin (DOX), a widely used chemotherapeutic agent, can potentiate immune checkpoint blockade in murine tumor models...
April 2018: Science Advances
https://www.readbyqxmd.com/read/29674509/antigen-presentation-keeps-trending-in-immunotherapy-resistance
#10
Anusha Kalbasi, Antoni Ribas
Through a gain-of-function kinome screen, MEX3B was identified as a mediator of resistance to T cell immunotherapy not previously identified using CRISPR based screens. MEX3B is a post-transcriptional regulator of HLA-A, validating the critical role of tumor-intrinsic antigen presentation in T cell immunotherapy and indicating a new putative molecular target.
April 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29674474/genetic-deletion-of-il-interleukin-19-exacerbates-atherogenesis-in-il19-%C3%A3-ldlr-double-knockout-mice-by-dysregulation-of-mrna-stability-protein-hur-human-antigen-r
#11
Mitali Ray, Khatuna Gabunia, Christine N Vrakas, Allison B Herman, Farah Kako, Sheri E Kelemen, Laurel A Grisanti, Michael V Autieri
OBJECTIVE: To test the hypothesis that loss of IL (interleukin)-19 exacerbates atherosclerosis. APPROACH AND RESULTS: Il19 -/- mice were crossed into Ldlr -/- (low-density lipoprotein receptor knock out) mice. Double knockout (dKO) mice had increased plaque burden in aortic arch and root compared with Ldlr -/- controls after 14 weeks of high-fat diet (HFD). dKO mice injected with 10 ng/g per day rmIL-19 had significantly less plaque compared with controls. qRT-PCR and Western blot analysis revealed dKO mice had increased systemic and intraplaque polarization of T cells and macrophages to proinflammatory Th 1 and M1 phenotypes, and also significantly increased TNF (tumor necrosis factor)-α expression in spleen and aortic arch compared with Ldlr -/- controls...
April 19, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29674422/a-perspective-on-the-evolving-story-of-psma-biology-and-psma-based-imaging-and-endoradiotherapeutic-strategies
#12
Denise S O'Keefe, Dean J Bacich, Steve S Huang, Warren D Heston
We will review the evolution of knowledge of the biology of Prostate-Specific Membrane Antigen (PSMA) and how the translation to therapy has also developed. The usual key to discovery is a realistic model for experimentation and hypothesis testing. This is especially true for the prostate where the human prostate differs significantly from that of other often used species for research models. We will emphasize the genetic characterization of PSMA, The nature of the PSMA protein and its role as a carboxypeptidase, with differing important substrates and products in different tissues...
April 19, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29673952/expression-of-c19mc-mirnas-in-hcc-associates-with-stem-cell-features-and-the-cancer-testis-genes-signature
#13
Claudia Augello, Federico Colombo, Andrea Terrasi, Elena Trombetta, Marco Maggioni, Laura Porretti, Giorgio Rossi, Silvana Guerneri, Rosamaria Silipigni, Silvano Bosari, Valentina Vaira
BACKGROUND: Intratumor heterogeneity of hepatocellular carcinoma (HCC) and, among HCC cell subsets, the cancer stem cell population (hCSC), is responsible for therapeutic resistance and disease relapse. AIMS: To characterize hCSC-enriched HCCs at the molecular level. METHODS: Side population (SP) was used to identify the hCSCs in multiple tumor sampling from different patients and primary HCCs cultures. FACS was used to immunoprofile cultures...
March 30, 2018: Digestive and Liver Disease
https://www.readbyqxmd.com/read/29673667/the-role-of-preoperative-serum-cancer-antigen-125-in-malignant-ovarian-germ-cell-tumors
#14
Ju-Hyun Kim, Jeong-Yeol Park, Jong-Hyeok Kim, Yong-Man Kim, Young-Tak Kim, Joo-Hyun Nam
OBJECTIVE: To determine the role of preoperative serum cancer antigen 125 (CA 125) in malignant ovarian germ cell tumors (MOGCTs). MATERIALS AND METHODS: Using information from medical databases of Asan Medical Center (Seoul, Korea), we investigated 161 patients with histologically diagnosed MOGCTs and whose preoperative serum CA 125 had been checked. We determined the optimal cutoff value of CA 125 as > 249.5 U/mL in MOGCTs using a receiver operating characteristic curve...
April 2018: Taiwanese Journal of Obstetrics & Gynecology
https://www.readbyqxmd.com/read/29673336/ab0-blood-groups-and-rhesus-factor-expression-as-prognostic-parameters-in-patients-with-epithelial-ovarian-cancer-a-retrospective-multi-centre-study
#15
Veronika Seebacher, Stephan Polterauer, Alexander Reinthaller, Heinz Koelbl, Regina Achleitner, Astrid Berger, Nicole Concin
BACKGROUND: AB0 blood groups and Rhesus factor expression have been associated with carcinogenesis, response to treatment and tumor progression in several malignancies. The aim of the present study was to test the hypothesis that AB0 blood groups and Rhesus factor expression are associated with clinical outcome in patients with epithelial ovarian cancer (EOC). METHODS: AB0 blood groups and Rhesus factor expression were evaluated in a retrospective multicenter study including 518 patients with EOC...
April 19, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29672807/imaging-to-differentiate-the-various-forms-of-seronegative-arthritis
#16
Iris Eshed, Kay-Geert A Hermann, Anna Zejden, Iwona Sudoł-Szopińska
Spondyloarthritis (SpA) is a group of diseases characterized by back pain, spinal inflammation, human leukocyte antigen-B27 positivity, and peripheral findings such as dactylitis, enthesitis, and uveitis. It includes ankylosing spondylitis, psoriatic arthritis, reactive arthritis, arthritis associated with inflammatory bowel disease, and undifferentiated SpA. The role of imaging in the diagnosis, management, and follow-up of patients with SpA has become dramatically more important with the introduction of new therapies such as tumor necrosis factor-α inhibitors...
April 2018: Seminars in Musculoskeletal Radiology
https://www.readbyqxmd.com/read/29672601/expression-of-immune-checkpoint-regulators-cytotoxic-t-lymphocyte-antigen-4-ctla-4-and-programmed-death-ligand-1-pd-l1-in-female-breast-carcinomas
#17
Ari Kassardjian, Peter I Shintaku, Neda A Moatamed
BACKGROUND: Immune checkpoint regulators, cytotoxic T lymphocyte antigen 4 (CTLA-4) and the programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1) have emerged as promising new targets for cancer therapeutics. While tumor expression of PD-L1 has been shown to have objective responses to anti-PD-L1 immunotherapies, the clinical implications of CTLA-4 expression in tumor cells or immune cells in the tumor microenvironment is still controversial. We investigated the expression of CTLA-4 and PD-L1 in human breast tumors and provided a scoring system for the systematic evaluation of CTLA-4 staining...
2018: PloS One
https://www.readbyqxmd.com/read/29672594/type-i-interferon-signaling-attenuates-regulatory-t-cell-function-in-viral-infection-and-in-the-tumor-microenvironment
#18
Arunakumar Gangaplara, Craig Martens, Eric Dahlstrom, Amina Metidji, Ameya S Gokhale, Deborah D Glass, Maria Lopez-Ocasio, Rachel Baur, Kishore Kanakabandi, Stephen F Porcella, Ethan M Shevach
Regulatory T cells (Tregs) play a cardinal role in the immune system by suppressing detrimental autoimmune responses, but their role in acute, chronic infectious diseases and tumor microenvironment remains unclear. We recently demonstrated that IFN-α/β receptor (IFNAR) signaling promotes Treg function in autoimmunity. Here we dissected the functional role of IFNAR-signaling in Tregs using Treg-specific IFNAR deficient (IFNARfl/flxFoxp3YFP-Cre) mice in acute LCMV Armstrong, chronic Clone-13 viral infection, and in tumor models...
April 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29672587/functional-relevance-of-in-vivo-half-antibody-exchange-of-an-igg4-therapeutic-antibody-drug-conjugate
#19
Peter Herbener, Kurt Schönfeld, Martin König, Matthias Germer, Jude M Przyborski, Katrin Bernöster, Jörg Schüttrumpf
An increasing number of monoclonal antibodies and derivatives such as antibody-drug conjugates (ADC) are of the IgG1 and IgG4 isotype with distinct structural and functional properties. In cases where antibody-mediated cytotoxicity is not desired, IgG4 is often used, as its Fc region is relatively poor at inducing antibody-dependent cell-mediated or complement-dependent cytotoxicity. IgG4 ADCs with highly cytotoxic drugs against proliferating target cells but which lack or have diminished antibody effector functions against quiescent cells may have a favorable safety profile compared to IgG1...
2018: PloS One
https://www.readbyqxmd.com/read/29672572/colorectal-cancer-and-cryptosporidium-spp-infection
#20
Violetta Sulżyc-Bielicka, Lidia Kołodziejczyk, Sylwia Jaczewska, Dariusz Bielicki, Krzysztof Safranow, Paweł Bielicki, Józef Kładny, Wojciech Rogowski
Transient or constant impaired immunity is often associated with neoplastic disease or oncological treatment. Among the most common pathogens found in patients with HIV or patients undergoing chemotherapy are protozoans of the Cryptosporidium genus, which cause diarrhea in humans and animals. The present study determined the frequency of Cryptosporidium spp. infections in patients with colorectal cancer (N = 108; 42 women; 66 men; median age, 65 years), before beginning oncological treatment, compared to a control group (N = 125; 56 women, 69 men; median age, 63 years) without colorectal cancer or a history of oncological disease...
2018: PloS One
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