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https://www.readbyqxmd.com/read/28342824/development-of-car-t-cells-designed-to-improve-antitumor-efficacy-and-safety
#1
REVIEW
Janneke E Jaspers, Renier J Brentjens
Chimeric antigen receptor (CAR) T cell therapy has shown promising efficacy against hematologic malignancies. Antitumor activity of CAR T cells, however, needs to be improved to increase therapeutic efficacy in both hematologic and solid cancers. Limitations to overcome are 'on-target, off-tumor' toxicity, antigen escape, short CAR T cell persistence, little expansion, trafficking to the tumor and inhibition of T cell activity by an inhibitory tumor microenvironment. Here we will discuss how optimizing the design of CAR T cells through genetic engineering addresses these limitations and improves the antitumor efficacy of CAR T cell therapy in pre-clinical models...
March 22, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28342665/recombinant-newcastle-disease-virus-expressing-the-infectious-bronchitis-virus-s1-gene-protects-chickens-against-newcastle-disease-virus-and-infectious-bronchitis-virus-challenge
#2
Ran Zhao, Junfeng Sun, Tianming Qi, Wen Zhao, Zongxi Han, Xiaopu Yang, Shengwang Liu
The recombinant LaSota strain expressing a chimeric IBV S1 gene (rLaSota-S1) was constructed with the S1 gene of the LX4 type IBV ck/CH/LDL/091022. The expression of the S1 protein was detected by an indirect immunofluorescence assay and Western blotting. The rLaSota-S1 strain was slightly attenuated, and its growth dynamics were similar to that of the parental LaSota strain. Vaccination of specific pathogen-free chickens with the rLaSota-S1 strain induced NDV hemagglutination inhibition antibodies, and it protected chickens from challenge with virulent NDV...
March 22, 2017: Vaccine
https://www.readbyqxmd.com/read/28339605/uniparental-chicken-offsprings-derived-from-oogenesis-of-chicken-primordial-germ-cells-zz-%C3%A2
#3
Chunhai Liu, Il-Kuk Chang, Kamal A Khazanehdari, Shruti Thomas, Preetha Varghese, Vijaya Baskar, Razan Alkhatib, Wenhai Li, Jörg Kinne, Michael J McGrew, Ulrich Wernery
Cloning (somatic cell nuclear transfer) in avian species has proven unachievable due to the physical structure of the avian oocyte. Here, the sexual differentiation of primordial germ cells with genetic sex ZZ (ZZ PGCs) was investigated in female germline chimeric chicken hosts with the aim to produce uniparental offspring. ZZ PGCs were expanded in culture and transplanted into the same and opposite sex chicken embryos which were partially sterilized using irradiation. All tested chimeric roosters (ZZ/ZZ) showed germline transmission with transmission rates of 3...
February 2, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28337888/decitabine-treatment-for-acute-myeloid-leukemia-relapse-after-allogeneic-hematopoietic-stem-cell-transplantation
#4
X L Liu, X Zhao, C Wang, S J Gao, Y H Tan
Therapeutic options for patients with relapse of acute myeloid leukemia (AML) after allo-SCT are limited. Here, we present a case of a 49-year female with AML who underwent myeloablative allo-SCT from a matched sibling donor. Seven months after transplantation she developed cGVHD and suffered from extramedullary plus concurrent medullary relapse. The presence of CNS extramedullary disease is unique. Our patient was treated with decetabine. After one cycle the patient achieved complete remission and full donor chimerism without severe side effects or the occurrence of GVHD...
January 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28337172/bone-marrow-derived-cell-accumulation-in-the-spinal-cord-is-independent-of-peripheral-mobilization-in-a-mouse-model-of-amyotrophic-lateral-sclerosis
#5
Kyle Peake, John Manning, Coral-Ann Lewis, Kevin Tran, Fabio Rossi, Charles Krieger
Bone marrow-derived cells (BMDCs) are capable of migrating across the blood-brain barrier (BBB) and accumulating in the central nervous system (CNS) when transplanted into recipients conditioned with whole-body irradiation or chemotherapy. We used the chemotherapeutic agents busulfan and treosulfan to condition recipient mice for transplantation with bone marrow (BM) cells isolated from donor mice ubiquitously expressing green fluorescent protein. We attempted to increase the accumulation of BMDCs in the CNS by mobilization of BMDCs using either, or both, granulocyte colony-stimulating factor (GCSF) or plerixafor (AMD3100)...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28336908/early-chimerism-after-liver-transplantation-reflects-the-clinical-course-of-recurrent-hepatitis-c
#6
Masashi Utsumi, Akinobu Takaki, Yuzo Umeda, Kazuko Koike, Stephanie C Napier, Nobukazu Watanabe, Susumu Shinoura, Ryuichi Yoshida, Daisuke Nobuoka, Tetsuya Yasunaka, Takahiro Oto, Motoo Araki, Kazuhide Yamamoto, Toshiyoshi Fujiwara, Takahito Yagi
BACKGROUND Human leukocyte antigen (HLA) mismatch is a characteristic feature of post-orthotopic liver transplantation (OLT) hepatitis C. To investigate the importance of donor HLA-restricted immune cells in post-OLT hepatitis C recurrence, we analyzed the frequency of donor chimerism and the clinical course of post-OLT hepatitis C. MATERIAL AND METHODS We analyzed peripheral blood chimerism in 11 HCV-reinfected patients with post-HLA mismatched OLT. Patients were divided into 2 groups: the OLT chronic hepatitis C (CHC) group (n=8), exhibiting active hepatitis C recurrence; and the OLT-persistently normal ALT (PNALT) group (n=3), without active hepatitis...
March 24, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28336069/a-highly-sensitive-biosensor-for-atp-using-a-chimeric-firefly-luciferase
#7
Bruce R Branchini, Tara L Southworth
Firefly luciferases, which emit visible light in a highly specific ATP-dependent process, have been adapted for a variety of applications based on the detection of the enzymes or using the proteins to measure ATP levels. Based on studies of chimeric luciferases, we engineered a novel luciferase called PLG2 that has enhanced specific activity, and thermal and pH stability compared to the commonly used Photinus pyralis luciferase. We present here protocols for preparing a single assay mixture containing PLG2 that can be used to readily detect femtomole levels of ATP...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28335327/targeting-at-the-nanoscale-a-novel-s-layer-fusion-protein-enabling-controlled-immobilization-of-biotinylated-molecules
#8
Melinda Varga
With the aim of constructing an S-layer fusion protein that combines both excellent self-assembly and specific ligand i.e., biotin binding ability, streptavidin (aa 16-133) was fused to the S-layer protein of Sporosarcina ureae ATCC 13881 (SslA) devoid of its N-terminal 341 and C-terminal 172 amino acids. The genetically engineered chimeric protein could be successfully produced in E. coli, isolated, and purified via Ni affinity chromatography. In vitro recrystallisation experiments performed with the purified chimeric protein in solution and on a silicon wafer have demonstrated that fusion of the streptavidin domain does not interfere with the self-assembling properties of the S-layer part...
November 4, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28334971/expanding-glycosaminoglycan-chemical-space-towards-the-creation-of-sulfated-analogs-novel-polymers-and-chimeric-constructs
#9
Rachel S Lane, Kalib St Ange, Behnam Zolghadr, Xinyue Liu, Christina Schäffer, Robert J Linhardt, Paul L DeAngelis
Glycosaminoglycans (GAGs) have therapeutic potential in areas ranging from angiogenesis, inflammation, hemostasis and cancer. GAG bioactivity is conferred by intrinsic structural features, such as disaccharide composition, glycosidic linkages and sulfation pattern. Unfortunately, the in vitro enzymatic synthesis of defined GAGs is quite restricted by a limited understanding of current GAG synthases and modifying enzymes. Our work provides insights into GAG-active enzymes through the creation of sulfated oligosaccharides, a new polysaccharide and chimeric polymers...
March 17, 2017: Glycobiology
https://www.readbyqxmd.com/read/28334881/random-pseuoduridylation-in-vivo-reveals-critical-region-of-escherichia-coli-23s-rrna-for-ribosome-assembly
#10
Margus Leppik, Aivar Liiv, Jaanus Remme
Pseudouridine is the most common modified nucleoside in RNA, which is found in stable RNA species and in eukaryotic mRNAs. Functional analysis of pseudouridine is complicated by marginal effect of its absence. We demonstrate that excessive pseudouridines in rRNA inhibit ribosome assembly. Ten-fold increase of pseudouridines in the 16S and 23S rRNA made by a chimeric pseudouridine synthase leads to accumulation of the incompletely assembled large ribosome subunits. Hyper modified 23S rRNA is found in the r-protein assembly defective particles and are selected against in the 70S and polysome fractions showing modification interference...
March 7, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28333325/triple-paternal-contribution-to-a-normal-complete-molar-chimeric-singleton-placenta
#11
I Ariel, D Goldman-Wohl, S Yagel, E Gazit, R Loewenthal
A comprehensive study of unusual cases of placental pathology may provide insight into mechanisms of normal human fertilization and early embryonic development by examining the exception to the rule. A gravida three para two 39-year-old woman was monitored by ultrasound from 16 weeks of gestation for cystic placenta. A female newborn was born at 36 weeks gestation. Pathologic examination of the partially cystic placenta revealed a singleton placenta comprised of 2/3 normal placenta and 1/3 complete hydatidiform mole, largely degenerated...
March 14, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28332949/public-attitudes-in-japan-towards-human-animal-chimeric-embryo-research-using-human-induced-pluripotent-stem-cells
#12
Tsutomu Sawai, Taichi Hatta, Misao Fujita
AIM: To understand the steps and objectives for which Japanese people are willing to accept human-animal chimeric embryo research using human induced pluripotent stem cells. METHODS: An internet-based survey was conducted for the general public and researchers in Japan in 2016. RESULTS: Over 60% of the public and 83.8% of researchers supported the creation of human-swine chimeras and 81.0% of the public and 92.4% of researchers supported the creation of human-swine chimeric embryos...
March 2, 2017: Regenerative Medicine
https://www.readbyqxmd.com/read/28332837/molecular-recognition-based-dna-nanoassemblies-on-the-surfaces-of-nanosized-exosomes
#13
Shuo Wan, Liqin Zhang, Sai Wang, Yuan Liu, Cuichen Wu, Cheng Cui, Hao Sun, Muling Shi, Ying Jiang, Long Li, Liping Qiu, Weihong Tan
Exosomes are membrane-enclosed extracellular vesicles derived from cells, carrying biomolecules that include pro-teins and nucleic acids for intercellular communication. Owning to their advantages of size, structure, stability and biocompatibility, exosomes have been used widely as natu-ral nanocarriers for intracellular delivery of theranostic agents. Meanwhile, surface modifications needed to endow exosomes with additional functionalities remain challeng-ing by their small size and the complexity of their mem-brane surfaces...
March 23, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28332318/a-novel-bispecific-molecule-delivered-by-recombinant-aav2-suppresses-ocular-inflammation-and-choroidal-neovascularization
#14
Yiming Li, Ping Zhu, Amrisha Verma, Tuhina Prasad, Hongxin Deng, Dechao Yu, Qiuhong Li
Elevated vascular endothelial growth factor (VEGF) and complement activation are implicated in the pathogenesis of different ocular diseases. The objective of this study was to investigate the hypothesis that dual inhibition of both VEGF and complement activation would confer better protection against ocular inflammation and neovascularization. In this study, we engineered a secreted chimeric VEGF inhibitor domain (VID), a complement inhibitor domain (CID) and a dual inhibitor (ACVP1). Vectors expressing these three inhibitors were constructed and packaged into AAV2 (sextY-F) particles...
March 22, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28332312/antitumor-activity-of-chlpmab-2-a-human-mouse-chimeric-cancer-specific-antihuman-podoplanin-antibody-via-antibody-dependent-cellular-cytotoxicity
#15
Mika K Kaneko, Shinji Yamada, Takuro Nakamura, Shinji Abe, Yasuhiko Nishioka, Akiko Kunita, Masashi Fukayama, Yuki Fujii, Satoshi Ogasawara, Yukinari Kato
Human podoplanin (hPDPN), a platelet aggregation-inducing transmembrane glycoprotein, is expressed in different types of tumors, and it binds to C-type lectin-like receptor 2 (CLEC-2). The overexpression of hPDPN is involved in invasion and metastasis. Anti-hPDPN monoclonal antibodies (mAbs) such as NZ-1 have shown antitumor and antimetastatic activities by binding to the platelet aggregation-stimulating (PLAG) domain of hPDPN. Recently, we developed a novel mouse anti-hPDPN mAb, LpMab-2, using the cancer-specific mAb (CasMab) technology...
March 23, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28332262/haploidentical-peripheral-blood-stem-cell-transplantation-without-irradiation-or-busulfan-after-reduced-intensity-conditioning-for-kmt2a-mll-rearranged-infant-b-cell-precursor-acute-lymphoblastic-leukemia-report-of-two-cases
#16
Ai Yoshimi, Keisuke Kato, Sho Hosaka, Ryoko Suzuki, Hiroko Fukushima, Tomohei Nakao, Chie Kobayashi, Takashi Fukushima, Kazutoshi Koike, Ryo Sumazaki, Masahiro Tsuchida
We present two infants with KMT2A(MLL)-gene-R-associated BCP-ALL, who received HLA haploidentical PBSCT after RIC. The patients developed ALL at age 6 months and 3 months, respectively. Case 1 underwent PBSCT at the second CR with detectable KMT2A-AFF1(MLL-AF4) fusion gene transcript at 11 months of age, and Case 2 at the first CR without KMT2A-MLLT1(MLL-ENL) fusion gene transcript at 8 months of age. Both patients received G-CSF-mobilized unmanipulated peripheral blood mononuclear cells from their HLA haploidentical mothers after administration of FLU, MEL, and ATG...
March 22, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28331617/current-approaches-to-increase-car-t-cell-potency-in-solid-tumors-targeting-the-tumor-microenvironment
#17
REVIEW
Irene Scarfò, Marcela V Maus
Chimeric antigen receptor (CAR) T-cell therapy represents a revolutionary treatment for haematological malignancies (i.e. B-ALL). However, the success of this type of treatment has not yet been achieved in solid tumors. One hypothesis is that the immunosuppressive nature of the tumor microenvironment (TME) influences and affects the efficacy of adoptive immunotherapy. Understanding the role of the TME and its interaction with CAR T-cells is crucial to improve the potency of adoptive immunotherapy. In this review, we discuss the strategies and potential combinatorial approaches recently developed in mouse models to enhance the efficacy of CAR T-cells, with particular emphasis on the translational potential of these approaches...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28331616/ex-vivo-akt-inhibition-promotes-the-generation-of-potent-cd19car-t-cells-for-adoptive-immunotherapy
#18
Ryan Urak, Miriam Walter, Laura Lim, ChingLam W Wong, Lihua E Budde, Sandra Thomas, Stephen J Forman, Xiuli Wang
BACKGROUND: Insufficient persistence and effector function of chimeric antigen receptor (CAR)-redirected T cells have been challenging issues for adoptive T cell therapy. Generating potent CAR T cells is of increasing importance in the field. Studies have demonstrated the importance of the Akt pathway in the regulation of T cell differentiation and memory formation. We now investigate whether inhibition of Akt signaling during ex vivo expansion of CAR T cells can promote the generation of CAR T cells with enhanced antitumor activity following adoptive therapy in a murine leukemia xenograft model...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28331184/the-long-non-coding-rna-linc01013-enhances-invasion-of-human-anaplastic-large-cell-lymphoma
#19
I-Hsiao Chung, Pei-Hsuan Lu, Yang-Hsiang Lin, Ming-Ming Tsai, Yun-Wen Lin, Chau-Ting Yeh, Kwang-Huei Lin
Anaplastic large-cell lymphoma (ALCL) is a rare type of highly malignant, non-Hodgkin lymphoma (NHL). Currently, only studies on the chimeric oncogene NPM-ALK have reported a link to ALCL progression. However, the specific molecular mechanisms underlying the invasion of ALCL are still unclear. Here, we sought to investigate differentially expressed, long non-coding RNAs (lncRNAs) in ALCL and their potential biological function. Our microarray analyses revealed that LINC01013, a novel non-coding RNA gene, was highly expressed in clinical specimens of ALCL and was significantly upregulated in invasive ALCL cell lines...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28331095/divergent-requirement-of-fc-fc%C3%AE-r-interactions-for-in-vivo-protection-against-influenza-viruses-by-two-pan-h5-hemagglutinin-antibodies
#20
Shuangshuang Wang, Huanhuan Ren, Wenbo Jiang, Honglin Chen, Hongxing Hu, Zhiwei Chen, Paul Zhou
Recent studies have shown that Fc-FcγR interactions are required for in vivo protection against influenza viruses by broadly reactive anti-HA stem, but not virus strain-specific, anti-receptor binding site (RBS), antibodies (Abs). Since only a few Abs recognizing epitopes in the head region but outside the RBS have been tested against single challenge virus strains, it remains unknown whether Fc-FcγR interactions are required for in vivo protection by Abs recognizing epitopes outside the RBS, and whether the requirement is virus strain-specific or epitope-specific...
March 22, 2017: Journal of Virology
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