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https://www.readbyqxmd.com/read/29150455/the-active-conformation-of-integrin-%C3%AE-7-may-be-a-multiple-myeloma-target
#1
(no author information available yet)
CAR T cells targeting active integrin β7 have cytotoxic activity against multiple myeloma (MM) cells.
November 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29147930/snp-association-study-in-pms2-associated-lynch-syndrome
#2
Sanne W Ten Broeke, Fadwa A Elsayed, Lisa Pagan, Maran J W Olderode-Berends, Encarna Gomez Garcia, Hans J P Gille, Liselot P van Hest, Tom G W Letteboer, Lizet E van der Kolk, Arjen R Mensenkamp, Theo A van Os, Liesbeth Spruijt, Bert J W Redeker, Manon Suerink, Yvonne J Vos, Anja Wagner, Juul T Wijnen, E W Steyerberg, Carli M J Tops, Tom van Wezel, Maartje Nielsen
Lynch syndrome (LS) patients are at high risk of developing colorectal cancer (CRC). Phenotypic variability might in part be explained by common susceptibility loci identified in Genome Wide Association Studies (GWAS). Previous studies focused mostly on MLH1, MSH2 and MSH6 carriers, with conflicting results. We aimed to determine the role of GWAS SNPs in PMS2 mutation carriers. A cohort study was performed in 507 PMS2 carriers (124 CRC cases), genotyped for 24 GWAS SNPs, including SNPs at 11q23.1 and 8q23.3...
November 17, 2017: Familial Cancer
https://www.readbyqxmd.com/read/29147628/trial-watch-adoptively-transferred-cells-for-anticancer-immunotherapy
#3
REVIEW
Carole Fournier, François Martin, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi, Lionel Apetoh
Immunotherapies aimed at strengthening immune effector responses against malignant cells are growing at exponential rates. Alongside, the impressive benefits obtained by patients with advanced melanoma who received adoptively transferred tumor-infiltrating lymphocytes (TILs) have encouraged the scientific community to pursue adoptive cell transfer (ACT)-based immunotherapy. ACT involves autologous or allogenic effector lymphocytes that are generally obtained from the peripheral blood or resected tumors, expanded and activated ex vivo, and administered to lymphodepleted patients...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29139002/deinococcus-multiflagellatus-sp-nov-isolated-from-a-car-air-conditioning-system
#4
Dong-Uk Kim, Hyosun Lee, Suyeon Lee, Sooyeon Park, Jung-Hoon Yoon, Lei Zhao, Min-Kyu Kim, Jae-Hyung Ahn, Jong-Ok Ka
A gamma radiation-resistant and pink-to-red pigmented bacterial strain, designated ID1504(T), was isolated from a car air-conditioning system sampled in Korea. The cells were observed to be Gram-stain negative, aerobic, motile with peritrichous flagella and short rod-shaped. Phylogenetically, the strain groups with the members of the genus Deinococcus and exhibits high 16S rRNA gene sequence similarities with Deinococcus arenae SA1(T) (94.0%), Deinococcus actinosclerus BM2(T) (93.9%) and Deinococcus soli N5(T) (93...
November 14, 2017: Antonie Van Leeuwenhoek
https://www.readbyqxmd.com/read/29133316/study-protocol-for-think-a-multinational-open-label-phase-i-study-to-assess-the-safety-and-clinical-activity-of-multiple-administrations-of-nkr-2-in-patients-with-different-metastatic-tumour-types
#5
Caroline Lonez, Bikash Verma, Alain Hendlisz, Philippe Aftimos, Ahmad Awada, Eric Van Den Neste, Gaetan Catala, Jean-Pascal H Machiels, Fanny Piette, Jason B Brayer, David A Sallman, Tessa Kerre, Kunle Odunsi, Marco L Davila, David E Gilham, Frédéric F Lehmann
INTRODUCTION: NKR-2 are autologous T cells genetically modified to express a chimeric antigen receptor (CAR) comprising a fusion of the natural killer group 2D (NKG2D) receptor with the CD3ζ signalling domain, which associates with the adaptor molecule DNAX-activating protein of 10 kDa (DAP10) to provide co-stimulatory signal upon ligand binding. NKG2D binds eight different ligands expressed on the cell surface of many tumour cells and which are normally absent on non-neoplastic cells...
November 12, 2017: BMJ Open
https://www.readbyqxmd.com/read/29132473/-progress-in-clinical-studies-of-chimeric-antigen-receptor-engineered-t-cells-for-treatment-of-childhood-cancer
#6
Ya-Ru Ni, Xiao-Jun Xu, Yong-Min Tang
Nowadays, the 5-year survival rate of childhood cancer patients can be more than 80%, but some patients with relapse and refractory cancers have shown no good response to traditional strategies. Chimeric antigen receptor engineered T (CAR-T) cell therapy is promising for these patients. CAR-T cells recognize the tumor-associated antigens in a non-major histocompatibility complex-restricted manner, so their anti-tumor ability is enhanced. There are four generations of CAR-T cells now. The complete remission rate of pediatric patients with relapse and refractory acute lymphoblastic leukemia can be as high as 90% when treated with CD19-targeting CAR-T cells...
November 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/29132013/chimeric-antigen-receptor-modified-t-cells-redirected-to-epha2-for-the-immunotherapy-of-non-small-cell-lung-cancer
#7
Ning Li, Shaohui Liu, Mingjiao Sun, Wei Chen, Xiaogang Xu, Zhu Zeng, Yemin Tang, Yongquan Dong, Alex H Chang, Qiong Zhao
Erythropoietin-producing hepatocellular carcinoma A2 (EphA2) is overexpressed in more than 90% of non-small cell lung cancer (NSCLC) but not significantly in normal lung tissue. It is therefore an important tumor antigen target for chimeric antigen receptors (CAR)-T-based therapy in NSCLC. Here, we developed a specific CAR targeted to EphA2, and the anti-tumor effects of this CAR were investigated. A second generation CAR with co-stimulatory receptor 4-1BB targeted to EphA2 was developed. The functionality of EphA2-specific T cells in vitro was tested with flow cytometry and real-time cell electronic sensing system assays...
November 10, 2017: Translational Oncology
https://www.readbyqxmd.com/read/29131157/targeting-the-t-cell-receptor-%C3%AE-chain-constant-region-for-immunotherapy-of-t-cell-malignancies
#8
Paul M Maciocia, Patrycja A Wawrzyniecka, Brian Philip, Ida Ricciardelli, Ayse U Akarca, Shimobi C Onuoha, Mateusz Legut, David K Cole, Andrew K Sewell, Giuseppe Gritti, Joan Somja, Miguel A Piris, Karl S Peggs, David C Linch, Teresa Marafioti, Martin A Pule
Mature T cell cancers are typically aggressive, treatment resistant and associated with poor prognosis. Clinical application of immunotherapeutic approaches has been limited by a lack of target antigens that discriminate malignant from healthy (normal) T cells. Unlike B cell depletion, pan-T cell aplasia is prohibitively toxic. We report a new targeting strategy based on the mutually exclusive expression of T cell receptor β-chain constant domains 1 and 2 (TRBC1 and TRBC2). We identify an antibody with unique TRBC1 specificity and use it to demonstrate that normal and virus-specific T cell populations contain both TRBC1(+) and TRBC2(+) compartments, whereas malignancies are restricted to only one...
November 13, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29127433/targeting-and-suppression-of-her3-positive-breast-cancer-by-t-lymphocytes-expressing-a-heregulin-chimeric-antigen-receptor
#9
Bai-Le Zuo, Bo Yan, Guo-Xu Zheng, Wen-Jin Xi, Xiao Zhang, An-Gang Yang, Lin-Tao Jia
Chimeric antigen receptor-modulated T lymphocytes (CAR-T) have emerged as a powerful tool for arousing anticancer immunity. Endogenous ligands for tumor antigen may outperform single-chain variable fragments to serve as a component of CARs with high cancer recognition efficacy and minimized immunogenicity. As heterodimerization and signaling partners for human epidermal growth factor receptor 2 (HER2), HER3/HER4 has been implicated in tumorigenic signaling and therapeutic resistance of breast cancer. In this study, we engineered T cells with a CAR consisting of the extracellular domain of heregulin-1β (HRG1β) that is a natural ligand for HER3/HER4, and evaluated the specific cytotoxicity of these CAR-T cells in cultured HER3 positive breast cancer cells and xenograft tumors...
November 10, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29126914/targeting-immuno-metabolism-to-improve-anti-cancer-therapies
#10
Kevin Beezhold, Craig A Byersdorfer
The immunology community has made significant strides in recent years in using the immune system to target and eliminate cancer. Therapies such as hematopoietic stem cell transplantation (HSCT) are the standard of care treatment for several malignancies, while therapies incorporating chimeric antigen receptor (CAR) T cells or checkpoint molecule blockade have been revolutionary. However, these approaches are not optimal for all cancers and in some cases, have failed outright. The greatest obstacle to making these therapies more effective may be rooted in one of the most basic concepts of cell biology, metabolism...
November 7, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29123951/characterization-of-a-switchable-chimeric-antigen-receptor-platform-in-a-pre-clinical-solid-tumor-model
#11
Elham Pishali Bejestani, Marc Cartellieri, Ralf Bergmann, Armin Ehninger, Simon Loff, Michael Kramer, Johannes Spehr, Antje Dietrich, Anja Feldmann, Susann Albert, Martin Wermke, Michael Baumann, Mechthild Krause, Martin Bornhäuser, Gerhard Ehninger, Michael Bachmann, Malte von Bonin
The universal modular chimeric antigen receptor (UniCAR) platform redirects CAR-T cells using a separated, soluble targeting module with a short half-life. This segregation allows precise controllability and flexibility. Herein we show that the UniCAR platform can be used to efficiently target solid cancers in vitro and in vivo using a pre-clinical prostate cancer model which overexpresses prostate stem cell antigen (PSCA). Short-term administration of the targeting module to tumor bearing immunocompromised mice engrafted with human UniCAR-T cells significantly delayed tumor growth and prolonged survival of recipient mice both in a low and high tumor burden model...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29123516/avidity-and-bystander-suppressive-capacity-of-human-regulatory-t-cells-expressing-de-novo-autoreactive-t-cell-receptors-in-type-1-diabetes
#12
Wen-I Yeh, Howard R Seay, Brittney Newby, Amanda L Posgai, Filipa Botelho Moniz, Aaron Michels, Clayton E Mathews, Jeffrey A Bluestone, Todd M Brusko
The ability to alter antigen specificity by T-cell receptor (TCR) or chimeric antigen receptor (CAR) gene transfer has facilitated personalized cellular immune therapies in cancer. Inversely, this approach can be harnessed in autoimmune settings to attenuate inflammation by redirecting the specificity of regulatory T cells (Tregs). Herein, we demonstrate efficient protocols for lentiviral gene transfer of TCRs that recognize type 1 diabetes-related autoantigens with the goal of tissue-targeted induction of antigen-specific tolerance to halt β-cell destruction...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29120743/staphylococcus-aureus-epicutaneous-exposure-drives-skin-inflammation-via-il-36-mediated-t-cell-responses
#13
Haiyun Liu, Nathan K Archer, Carly A Dillen, Yu Wang, Alyssa G Ashbaugh, Roger V Ortines, Tracy Kao, Steven K Lee, Shuting S Cai, Robert J Miller, Mark C Marchitto, Emily Zhang, Daniel P Riggins, Roger D Plaut, Scott Stibitz, Raif S Geha, Lloyd S Miller
Staphylococcus aureus colonization contributes to skin inflammation in diseases such as atopic dermatitis, but the signaling pathways involved are unclear. Herein, epicutaneous S. aureus exposure to mouse skin promoted MyD88-dependent skin inflammation initiated by IL-36, but not IL-1α/β, IL-18, or IL-33. By contrast, an intradermal S. aureus challenge promoted MyD88-dependent host defense initiated by IL-1β rather than IL-36, suggesting that different IL-1 cytokines trigger MyD88 signaling depending on the anatomical depth of S...
November 8, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/29119551/chimeric-antigen-receptor-transduced-t-cells-tuning-up-for-the-next-generation
#14
REVIEW
Maria-Luisa Schubert, Jean-Marc Hoffmann, Peter Dreger, Carsten Müller-Tidow, Michael Schmitt
Chimeric antigen receptor (CAR) T cell therapy has recently achieved impressive clinical outcome in patients with CD19-positive hematologic malignancies. Extrapolation of CAR T cell treatment to solid tumors, however, has not yet yielded similar results. This might be due to intrinsic causes, e.g. insufficient CAR T cell activation or CAR toxicity as well as extrinsic factors displaying an unfavorable tumor environment for CAR T cells by raising physical and chemical barriers. In this review, we discuss the advantages as well as major obstacles of CAR T cell therapy, particularly in the context of solid tumors, and focus on efforts and novel strategies in CAR T cell development...
November 9, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29118598/first-record-of-thecturota-tenuissima-casey-from-canada-coleoptera-staphylinidae-aleocharinae
#15
Jan Klimaszewski, Tim Struyve, Caroline Bourdon, Julie-Anne Dorval
Thecturota tenuissima Casey, is reported for the first time from Canada, based on records from Ontario and Quebec. It was originally described from Rhode Island, USA, and no other records of this species in North America were published since that time. The specimens from Canada were captured by car netting. We provide here a redescription of this species and never before published images of habitus, tergite, and sternite VIII of both sexes, median lobe of aedeagus and spermatheca. The features distinguishing T...
2017: ZooKeys
https://www.readbyqxmd.com/read/29118234/emerging-role-of-car-t-cells-in-non-hodgkin-s-lymphoma
#16
REVIEW
Mauro P Avanzi, Renier J Brentjens
Adoptive T-cell therapy with chimeric antigen receptor T cells (CAR-Ts) has produced impressive clinical responses among patients with B-cell malignancies, and several groups have published positive results using anti-CD19 CAR-Ts for the treatment of B-cell acute lymphoblastic leukemia. Recently, new data from clinical trials have demonstrated the benefits of CAR-T therapy in the non-Hodgkin's lymphoma (NHL) setting. This review describes some of the most recent and promising advances in engineered T-cell therapy, with particular emphasis on the clinical benefits of NHL treatment...
November 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29113977/fda-approves-second-car-t-cell-therapy
#17
(no author information available yet)
The FDA approved the chimeric antigen receptor T-cell therapy axicabtagene ciloleucel, making it the second such treatment for blood cancers in the United States. The therapy is indicated for adults with certain non-Hodgkin lymphomas who have tried at least two other treatments.
November 7, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29113941/human-relevance-of-rodent-liver-tumors-key-insights-from-a-toxicology-forum-workshop-on-nongenotoxic-modes-of-action
#18
Susan P Felter, Jennifer E Foreman, Alan Boobis, J Christopher Corton, Adriana M Doi, Lynn Flowers, Jay Goodman, Lynne T Haber, Abigail Jacobs, James E Klaunig, Angela M Lynch, Jonathan Moggs, Arun Pandiri
The Toxicology Forum sponsored a workshop in October 2016, on the human relevance of rodent liver tumors occurring via nongenotoxic modes of action (MOAs). The workshop focused on two nuclear receptor-mediated MOAs (Constitutive Androstane Receptor (CAR) and Peroxisome Proliferator Activated Receptor-alpha (PPARα), and on cytotoxicity. The goal of the meeting was to review the state of the science to (1) identify areas of consensus and differences, data gaps and research needs; (2) identify reasons for inconsistencies in current regulatory positions; and (3) consider what data are needed to demonstrate a specific MOA, and when additional research is needed to rule out alternative possibilities...
November 4, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/29112739/organophosphate-flame-retardants-alter-adult-mouse-homeostasis-and-gene-expression-in-a-sex-dependent-manner-potentially-through-interactions-with-er%C3%AE
#19
Elizabeth A Krumm, Vipa J Patel, Taylor S Tillery, Ali Yasrebi, Jianliang Shen, Grace L Guo, Stephanie M Marco, Brian T Buckley, Troy A Roepke
Flame retardants (FR) such as polybrominated diphenyl ethers (PBDE) and organophosphate FR (OPFR) persist in the environment and interact with multiple nuclear receptors involved in homeostasis, including estrogen receptors (ER). However, little is known about the effects of FR, especially OPFR, on mammalian neuroendocrine functions. Therefore, we investigated if exposure to FR alters hypothalamic gene expression and whole-animal physiology in adult wild-type (WT) and ERα KO mice. Intact WT and KO males and ovariectomized WT and KO females were orally dosed daily with vehicle (oil), 17α-ethynylestradiol (2...
November 3, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29110403/live-cell-labeling-with-novel-terpyridine-derivative-proligands-to-measure-cytotoxicity-mediated-by-immune-cells
#20
Yoshimasa Tanaka, Yuki Sakai, Satoshi Mizuta, Asuka Kumagai, Mohamed S O Tagod, Hiroaki Senju, Tatsufumi Nakamura, Craig T Morita
Immunotherapy using immune checkpoint inhibitors and CAR-T cells has revolutionized treatment for patients with malignant tumors. However, measuring tumor cell cytotoxicity mediated by immune effector cells in clinical laboratories has been difficult due to the requirement for radioactive substances. In this study, a series of novel terpyridine derivative proligands were synthesized and a non-radioactive cellular cytotoxicity assay using the newly synthesized compounds was developed for use in preclinical and clinical studies for cancer immunotherapy...
November 7, 2017: ChemMedChem
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