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https://www.readbyqxmd.com/read/28641074/development-of-novel-antigen-receptors-for-car-t-cell-therapy-directed-toward-solid-malignancies
#1
REVIEW
David Chen, James Yang
Development of chimeric antigen receptor (CAR) T cells have led to remarkable successes in the treatment of B-cell malignancies with anti-CD19 CAR. Here we discuss the development of novel antigen receptors for use in solid malignancies with respect to target antigens, receptor design, and T cell manipulations.
June 1, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28634010/lamp-1-chimeric-dna-vaccines-enhance-the-antibody-response-in-japanese-flounder-paralichthys-olivaceus
#2
Iang Rondón-Barragán, Reiko Nozaki, Ikuo Hirono, Hidehiro Kondo
DNA vaccination is one method to protect farmed fish from viral and bacterial diseases. Chimeric antigens encoded by DNA vaccines have been shown to increase the resistance to viral diseases. Here, we sequenced the gene encoding lysosome-associated membrane protein-1 from Japanese flounder, Paralichthys olivaceus, (JfLAMP-1) and assessed its use in a chimeric DNA vaccine fused with the major capsule protein (MCP) from red seabream iridovirus (RSIV). JfLAMP-1 cDNA has a length of 1248 bp encoding 415 aa, which contains transmembrane and cytoplasmic domains...
June 17, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28629762/targeting-the-tumor-and-its-associated-stroma-one-and-one-can-make-three-in-adoptive-t-cell-therapy-of-solid-tumors
#3
Anna Mondino, Gerlanda Vella, Laura Icardi
Adoptive T cell therapy (ACT) has become a promising immunotherapeutic option for cancer patients. The proof for ACT therapeutic efficacy was first obtained with allogenic T cells and then reproduced with T cells isolated from patients' tumor samples (i.e. tumor-infiltrating lymphocytes). It is now clear that specificity of ACT products can be educated by genetically engineering T cells with classical T Cell Receptors (TCR) or chimeric antigen receptors (CAR). To date a poor accessibility of the tumor mass and a hostile microenvironment, influenced by genetic and epigenetic instability, mainly limit ACT therapeutic efficacy in the case of solid tumors...
June 15, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28629761/cytokines-for-the-induction-of-antitumor-effectors-the-paradigm-of-cytokine-induced-killer-cik-cells
#4
Elisa Cappuzzello, Roberta Sommaggio, Paola Zanovello, Antonio Rosato
Cytokine-Induced killer (CIK) cells are raising growing interest in cellular antitumor therapy, as they can be easily expanded with a straightforward and inexpensive protocol, and are safe requiring only GMP-grade cytokines to obtain very high amounts of cytotoxic cells. CIK cells do not need antigen-specific stimuli to be activated and proliferate, as they recognize and destroy tumor cells in an HLA-independent fashion through the engagement of NKG2D. In several preclinical studies and clinical trials, CIK cells showed a reduced alloreactivity compared to conventional T cells, even when challenged across HLA-barriers; only in a few patients, a mild GVHD occurred after treatment with allogeneic CIK cells...
June 3, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28625826/drug-discovery-and-therapeutic-delivery-for-the-treatment-of-b-and-t-cell-tumors
#5
Regan Stephenson, Ankur Singh
Hematological malignancies manifest as lymphoma, leukemia, and myeloma, and remain a burden on society. From initial therapy to endless relapse-related treatment, societal burden is felt not only in the context of healthcare cost, but also in the compromised quality of life of patients. Long-term therapeutic strategies have become the standard in keeping hematological malignancies at bay as these cancers develop resistance to each round of therapy with time. As a result, there is a continual need for the development of new drugs to combat resistant disease in order to prolong patient life, if not to produce a cure...
June 15, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28625015/crispr-cas9-mediated-lag-3-disruption-in-car-t-cells
#6
Yongping Zhang, Xingying Zhang, Chen Cheng, Wei Mu, Xiaojuan Liu, Na Li, Xiaofei Wei, Xiang Liu, Changqing Xia, Haoyi Wang
T cells engineered with chimeric antigen receptor (CAR) have been successfully applied to treat advanced refractory B cell malignancy. However, many challenges remain in extending its application toward the treatment of solid tumors. The immunosuppressive nature of tumor microenvironment is considered one of the key factors limiting CAR-T efficacy. One negative regulator of Tcell activity is lymphocyte activation gene-3 (LAG-3). We successfully generated LAG-3 knockout Tand CAR-T cells with high efficiency using CRISPR-Cas9 mediated gene editing and found that the viability and immune phenotype were not dramatically changed during in vitro culture...
June 17, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28621670/analyses-of-a-whole-genome-inter-clade-recombination-map-of-hepatitis-delta-virus-suggest-a-host-polymerase-driven-and-viral-rna-structure-promoted-template-switching-mechanism-for-viral-rna-recombination
#7
Mei Chao, Tzu-Chi Wang, Chia-Chi Lin, Robert Yung-Liang Wang, Wen-Bin Lin, Shang-En Lee, Ying-Yu Cheng, Chau-Ting Yeh, Shan-Bei Iang
The genome of hepatitis delta virus (HDV) is a 1.7-kb single-stranded circular RNA that folds into an unbranched rod-like structure and has ribozyme activity. HDV redirects host RNA polymerase(s) (RNAP) to perform viral RNA-directed RNA transcription. RNA recombination is known to contribute to the genetic heterogeneity of HDV, but its molecular mechanism is poorly understood. Here, we established a whole-genome HDV-1/HDV-4 recombination map using two cloned sequences coexisting in cultured cells. Our functional analyses of the resulting chimeric delta antigens (the only viral-encoded protein) and recombinant genomes provide insights into how recombination promotes the genotypic and phenotypic diversity of HDV...
June 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28613086/exploiting-natural-killer-group-2d-receptors-for-car-t-cell-therapy
#8
Benjamin Demoulin, W James Cook, Joana Murad, David J Graber, Marie-Louise Sentman, Caroline Lonez, David E Gilham, Charles L Sentman, Sophie Agaugue
Chimeric antigen receptors (CARs) are genetically engineered proteins that combine an extracellular antigen-specific recognition domain with one or several intracellular T-cell signaling domains. When expressed in T cells, these CARs specifically trigger T-cell activation upon antigen recognition. While the clinical proof of principle of CAR T-cell therapy has been established in hematological cancers, CAR T cells are only at the early stages of being explored to tackle solid cancers. This special report discusses the concept of exploiting natural killer cell receptors as an approach that could broaden the specificity of CAR T cells and potentially enhance the efficacy of this therapy against solid tumors...
June 14, 2017: Future Oncology
https://www.readbyqxmd.com/read/28612701/neuraminidase-mediated-haemagglutination-of-recent-human-influenza-a-h3n2-viruses-is-determined-by-arginine-150-flanking-the-neuraminidase-catalytic-site
#9
Ramona Mögling, Mathilde J Richard, Stefan van der Vliet, Ruud van Beek, Eefje J A Schrauwen, Monique I Spronken, Guus F Rimmelzwaan, Ron A M Fouchier
Over the last decade, an increasing proportion of circulating human influenza A(H3N2) viruses exhibited haemagglutination activity that was sensitive to neuraminidase inhibitors. This change in haemagglutination as compared to older circulating A(H3N2) viruses prompted an investigation of the underlying molecular basis. Recent human influenza A(H3N2) viruses were found to agglutinate turkey erythrocytes in a manner that could be blocked with either oseltamivir or neuraminidase-specific antisera, indicating that agglutination was driven by neuraminidase, with a low or negligible contribution of haemagglutinin...
June 13, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28612394/tumor-associated-with-cd70-expression-is-involved-in-promoting-tumor-migration-and-macrophage-infiltration-in-gbm
#10
Haitao Ge, Luyan Mu, Linchun Jin, Changlin Yang, Yifan Emily Chang, Yu Long, Gabriel De Leon, Loic Deleyrolle, Duane A Mitchell, Paul S Kubilis, Dunyue Lu, Jiping Qi, Yunhe Gu, Zhiguo Lin, Jianping Huang
Tumor migration/metastasis and immunosuppression are major obstacles in effective cancer therapy. Incidentally, these 2 hurdles usually coexist inside tumors, therefore making therapy significantly more complicated, as both oncogenic mechanisms must be addressed for successful therapeutic intervention. Our recent report highlights that the tumor expression of a TNF family member, CD70, is correlated with poor survival for primary gliomas. In this study, we investigated how CD70 expression by GBM affects the characteristics of tumor cells and the tumor microenvironment...
June 13, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28611475/murine-lrba-deficiency-causes-ctla-4-deficiency-in-tregs-without-progression-to-immune-dysregulation
#11
Deborah Burnett, Ian Parish, Etienne Masle-Farquhar, Robert Brink, Christopher Goodnow
Inherited mutations in Lipopolysaccharide Responsive Beige-like Anchor (LRBA) cause a recessive human immune dysregulation syndrome with memory B cell and antibody deficiency (common variable immunodeficiency, CVID), inflammatory bowel disease, enlarged spleen and lymph nodes, accumulation of activated T cells, and multiple autoimmune diseases. To understand the pathogenesis of the syndrome, C57BL/6 mice carrying a homozygous truncating mutation in Lrba were produced using CRISPR/Cas9-mediated gene targeting...
June 14, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28610774/false-positive-hiv-nucleic-acid-amplification-testing-during-car-t-cell-therapy
#12
Ella J Ariza-Heredia, Bruno P Granwehr, George M Viola, Micah Bhatti, James M Kelley, James Kochenderfer, Chitra Hosing
Advancements in immunotherapy have opened a new era in oncology, to include genetic modification of human T-cells to express a chimeric antigen receptor (CAR) that enables targeted tumor recognition (Kochenderfer et al., 2015; Lee et al., 2015; Maus and Levine 2016; Rosenberg et al., 2008). Herein, we report a false-positive HIV testing in a patient who had undergone CAR T-cell therapy created with a lentiviral vector.
June 3, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/28608115/phase-i-trial-of-antigen-targeted-autologous-dendritic-cell-based-vaccine-with-in-vivo-activation-of-inducible-cd40-for-advanced-prostate-cancer
#13
Guru Sonpavde, John D McMannis, Yu Bai, Mamatha R Seethammagari, Joan M C Bull, Victoria Hawkins, Theresa K Dancsak, Natasha Lapteva, Jonathan M Levitt, Annemarie Moseley, David M Spencer, Kevin M Slawin
This phase I trial reports the safety and activity of BPX101, a second-generation antigen-targeted autologous antigen presenting cell (APC) vaccine in men with metastatic castration-resistant prostate cancer (mCRPC). To manufacture BPX101, APCs collected in a single leukapheresis were transduced with adenoviral vector Ad5f35 encoding inducible human (ih)-CD40, followed by incubation with protein PA001, which contains the extracellular domain of human prostate-specific membrane antigen. The ih-CD40 represents a modified chimeric version of the dendritic cell (DC) co-stimulatory molecule, CD40, which responds to a bioinert membrane-permeable activating dimerizer drug, rimiducid (AP1903), permitting temporally controlled, lymphoid-localized, DC-specific activation...
June 12, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28604239/continuing-challenges-and-current-issues-in-acute-lymphoblastic-leukemia
#14
Ankit Kansagra, Saurabh Dahiya, Mark Litzow
Conventional cytotoxic chemotherapy used to treat acute lymphoblastic leukemia (ALL) has resulted into high cure rates for pediatric patients, however outcomes for adult patients remain suboptimal. The 5-year overall survival is only 30-40% in adults and elderly patients with ALL compared to 90% in children. We have seen major advances in our understanding and management of ALL related to identification of new cytogenetic and molecular abnormalities and development of novel targeted agents for the treatment of ALL...
June 11, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28602436/car-t-cells-administered-in-combination-with-lymphodepletion-and-pd-1-inhibition-to-patients-with-neuroblastoma
#15
Andras Heczey, Chrystal U Louis, Barbara Savoldo, Olga Dakhova, April Durett, Bambi Grilley, Hao Liu, Mengfeng F Wu, Zhuyong Mei, Adrian Gee, Birju Mehta, Huimin Zhang, Nadia Mahmood, Haruko Tashiro, Helen E Heslop, Gianpietro Dotti, Cliona M Rooney, Malcolm K Brenner
Targeting disialoganglioside (GD2) on neuroblastoma (NB) with T cells expressing a first-generation chimeric antigen receptor (CAR) was safe, but the cells had poor expansion and long-term persistence. We developed a third-generation GD2-CAR (GD2-CAR3) and hypothesized that GD2-CAR3 T cells (CARTs) would be safe and effective. This phase 1 study enrolled relapsed or refractory NB patients in three cohorts. Cohort 1 received CART alone, cohort 2 received CARTs plus cyclophosphamide and fludarabine (Cy/Flu), and cohort 3 was treated with CARTs, Cy/Flu, and a programmed death-1 (PD-1) inhibitor...
June 8, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28596938/genome-edited-t-cell-therapies
#16
REVIEW
Juliette M K M Delhove, Waseem Qasim
PURPOSE OF REVIEW: Alternative approaches to conventional drug-based cancer treatments have seen T cell therapies deployed more widely over the last decade. This is largely due to their ability to target and kill specific cell types based on receptor recognition. Introduction of recombinant T cell receptors (TCRs) using viral vectors and HLA-independent T cell therapies using chimeric antigen receptors (CARs) are discussed. This article reviews the tools used for genome editing, with particular emphasis on the applications of site-specific DNA nuclease mediated editing for T cell therapies...
2017: Current Stem Cell Reports
https://www.readbyqxmd.com/read/28594388/gene-therapy-for-pancreatic-cancer-specificity-issues-and-hopes
#17
REVIEW
Marie Rouanet, Marine Lebrin, Fabian Gross, Barbara Bournet, Pierre Cordelier, Louis Buscail
A recent death projection has placed pancreatic ductal adenocarcinoma as the second cause of death by cancer in 2030. The prognosis for pancreatic cancer is very poor and there is a great need for new treatments that can change this poor outcome. Developments of therapeutic innovations in combination with conventional chemotherapy are needed urgently. Among innovative treatments the gene therapy offers a promising avenue. The present review gives an overview of the general strategy of gene therapy as well as the limitations and stakes of the different experimental in vivo models, expression vectors (synthetic and viral), molecular tools (interference RNA, genome editing) and therapeutic genes (tumor suppressor genes, antiangiogenic and pro-apoptotic genes, suicide genes)...
June 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28591403/preliminary-multiplex-microarray-igg-immunoassay-for-the-diagnosis-of-toxoplasmosis-and-rubella
#18
Priscila T Baschirotto, Marco A Krieger, Leonardo Foti
BACKGROUND: During pregnancy, toxoplasmosis and rubella can cause serious damage to the mother and the foetus through vertical transmission. Early diagnosis enables implementation of health measures aimed at preventing vertical transmission and minimising damage caused by these diseases. OBJECTIVE: Here, we report the development of a multiplex assay for simultaneous detection of IgG antibodies produced during toxoplasmosis and rubella infection. METHODS: This assay is based on xMap technology...
June 2017: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/28588060/sending-car-t-cells-after-multiple-myeloma
#19
(no author information available yet)
Preliminary results from an ongoing phase I clinical trial in China suggest that chimeric antigen receptor T cells engineered to home in on a protein called BCMA may be a potent therapeutic option for multiple myeloma. The therapy was well tolerated and induced complete, durable responses in patients with relapsed/refractory disease.
June 6, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28586488/use-of-chimeric-antigen-receptor-t-cells-as-a-potential-therapeutic-for-glioblastoma
#20
Muhammad Babar Khan, Shamik Chakraborty, John Andrew Boockvar
No abstract text is available yet for this article.
May 1, 2017: Neurosurgery
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