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adoptive cell transfer

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https://www.readbyqxmd.com/read/29792274/ex-vivo-expanded-natural-regulatory-t-cells-from-patients-with-end-stage-renal-disease-or-kidney-transplantation-are-useful-for-autologous-cell-therapy
#1
Sybille Landwehr-Kenzel, Anne Zobel, Henrike Hoffmann, Niels Landwehr, Michael Schmueck-Henneresse, Thomas Schachtner, Andy Roemhild, Petra Reinke
Novel concepts employing autologous, ex vivo expanded natural regulatory T cells (nTreg) for adoptive transfer has potential to prevent organ rejection after kidney transplantation. However, the impact of dialysis and maintenance immunosuppression on the nTreg phenotype and peripheral survival is not well understood, but essential when assessing patient eligibility. The current study investigates regulatory T-cells in dialysis and kidney transplanted patients and the feasibility of generating a clinically useful nTreg product from these patients...
June 2018: Kidney International
https://www.readbyqxmd.com/read/29791511/caspase-11-dependent-pyroptosis-of-lung-epithelial-cells-protects-from-melioidosis-while-caspase-1-mediates-macrophage-pyroptosis-and-production-of-il-18
#2
Jinyong Wang, Manoranjan Sahoo, Louis Lantier, Jonathan Warawa, Hector Cordero, Kelly Deobald, Fabio Re
Infection with Burkholderia pseudomallei or B. thailandensis triggers activation of the NLRP3 and NLRC4 inflammasomes leading to release of IL-1β and IL-18 and death of infected macrophages by pyroptosis, respectively. The non-canonical inflammasome composed of caspase-11 is also activated by these bacteria and provides protection through induction of pyroptosis. The recent generation of bona fide caspase-1-deficient mice allowed us to reexamine in a mouse model of pneumonic melioidosis the role of caspase-1 independently of caspase-11 (that was also absent in previously generated Casp1-/- mice)...
May 23, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29790621/generation-and-application-of-human-induced-stem-cell-memory-t-it-scm-cells-for-adoptive-immunotherapy
#3
Taisuke Kondo, Yuuki Imura, Shunsuke Chikuma, Sana Hibino, Setsuko Omata-Mise, Makoto Ando, Takashi Akanuma, Mana Iizuka, Ryota Sakai, Rimpei Morita, Akihiko Yoshimura
Adoptive T cell therapy is an effective strategy for cancer immunotherapy. However, infused T cells frequently become functionally exhausted, and consequently offer a poor prognosis after transplantation into patients. Adoptive transfer of tumor antigen-specific stem cell memory T (TSCM ) cells is expected to overcome this shortcoming since TSCM cells are close to naïve T cells, but are also highly proliferative, long-lived, and produce a large number of effector T cells in response to antigen stimulation...
May 23, 2018: Cancer Science
https://www.readbyqxmd.com/read/29789639/fludarabine-and-neurotoxicity-in-engineered-t-cell-therapy
#4
Kate L Lowe, Crystal L Mackall, Elliot Norry, Rafael Amado, Bent K Jakobsen, Gwendolyn Binder
Adoptive T-cell therapy, incorporating engineered T cell receptors (TCRs) or chimeric antigen receptors (CARs), target tumor antigens with high affinity and specificity. To increase the potency of adoptively transferred T cells, patients are conditioned with lymphodepleting chemotherapy regimens prior to adoptive T-cell transfer (ACT), and data suggest that fludarabine is an important component of an effective regimen. In a recent clinical trial using CAR-T cells engineered to target the CD19 B-cell antigen to treat acute lymphoblastic leukemia, JCAR-015 (NCT02535364), two patient deaths due to cerebral edema led to trial suspension...
May 7, 2018: Gene Therapy
https://www.readbyqxmd.com/read/29784012/treatment-of-experimental-colitis-by-endometrial-regenerative-cells-through-regulation-of-b-lymphocytes-in-mice
#5
Xiaoxi Xu, Yong Wang, Baoren Zhang, Xu Lan, Shanzheng Lu, Peng Sun, Xiang Li, Ganggang Shi, Yiming Zhao, Hongqiu Han, Caigan Du, Hao Wang
BACKGROUND: Endometrial regenerative cells (ERCs), a novel type of mesenchymal-like stem cell derived from menstrual blood, have been recently evaluated as an attractive candidate source in ulcerative colitis (UC); however, the mechanism is not fully understood. The present study was designed to investigate the effects of ERCs, especially on B-cell responses in UC. METHODS: In this study, colitis was induced by administering 3% dextran sodium sulfate (DSS) via free drinking water for 7 days to BALB/c mice...
May 22, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29783988/tolerogenic-bone-marrow-derived-dendritic-cells-induce-neuroprotective-regulatory-t-cells-in-a-model-of-parkinson-s-disease
#6
Charles R Schutt, Howard E Gendelman, R Lee Mosley
BACKGROUND: Administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) increases regulatory T cell (Treg) number and function with control of neuroinflammation and neuronal protection in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease (PD). Recently, we demonstrated in an early phase 1 clinical trial that GM-CSF also improves motor skills in PD patients. However, the mechanisms of Treg induction and its effects on neuroprotective responses remain unknown...
May 21, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29782541/an-unappreciated-role-for-neutrophil-dc-hybrids-in-immunity-to-invasive-fungal-infections
#7
J Scott Fites, Michael Gui, John F Kernien, Paige Negoro, Zeina Dagher, David B Sykes, Jeniel E Nett, Michael K Mansour, Bruce S Klein
Neutrophils are classically defined as terminally differentiated, short-lived cells; however, neutrophils can be long-lived with phenotypic plasticity. During inflammation, a subset of neutrophils transdifferentiate into a population called neutrophil-DC hybrids (PMN-DCs) having properties of both neutrophils and dendritic cells. While these cells ubiquitously appear during inflammation, the role of PMN-DCs in disease remains poorly understood. We observed the differentiation of PMN-DCs in pre-clinical murine models of fungal infection: blastomycosis, aspergillosis and candidiasis...
May 21, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29781999/preparation-of-murine-submandibular-salivary-gland-for-upright-intravital-microscopy
#8
Xenia Ficht, Flavian Thelen, Bettina Stolp, Jens V Stein
The submandibular salivary gland (SMG) is one of the three major salivary glands, and is of interest for many different fields of biological research, including cell biology, oncology, dentistry, and immunology. The SMG is an exocrine gland comprised of secretory epithelial cells, myofibroblasts, endothelial cells, nerves, and extracellular matrix. Dynamic cellular processes in the rat and mouse SMG have previously been imaged, mostly using inverted multi-photon microscope systems. Here, we describe a straightforward protocol for the surgical preparation and stabilization of the murine SMG in anesthetized mice for in vivo imaging with upright multi-photon microscope systems...
May 7, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29780461/-in-operando-imaging-of-self-catalyzed-formaldehyde-burst-in-methanol-oxidation-reactions-under-open-circuit-conditions
#9
Liang Yuan, Meng Li, Tinglian Yuan, Yimin Fang, Wei Wang
We employ a surface plasmon resonance imaging (SPRi) technique to monitor the in operando process of formaldehyde (HCHO) production during methanol oxidation with high spatial and temporal resolutions. While common wisdom suggests HCHO is generated as an intermediate during continuous electron transfer towards CO2 , we find that the majority of HCHO is produced via self-catalyzed chemical and electrochemical reactions under open-circuit conditions, which lead to an unprecedented HCHO burst immediately after withdrawal of external potential...
April 7, 2018: Chemical Science
https://www.readbyqxmd.com/read/29773802/cd4-t-cells-are-activated-in-regional-lymph-nodes-and-migrate-to-skin-to-initiate-lymphedema
#10
Gabriela D García Nores, Catherine L Ly, Daniel A Cuzzone, Raghu P Kataru, Geoffrey E Hespe, Jeremy S Torrisi, Jung Ju Huang, Jason C Gardenier, Ira L Savetsky, Matthew D Nitti, Jessie Z Yu, Sonia Rehal, Babak J Mehrara
T cell-mediated responses have been implicated in the development of fibrosis, impaired lymphangiogenesis, and lymphatic dysfunction in secondary lymphedema. Here we show that CD4+ T cells are necessary for lymphedema pathogenesis by utilizing adoptive transfer techniques in CD4 knockout mice that have undergone tail skin and lymphatic excision or popliteal lymph node dissection. We also demonstrate that T cell activation following lymphatic injury occurs in regional skin-draining lymph nodes after interaction with antigen-presenting cells such as dendritic cells...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29771253/axicabtagene-ciloleucel-for-the-treatment-of-relapsed-refractory-b-cell-non-hodgkin-s-lymphomas
#11
P Sharma, G T King, S S Shinde, E Purev, A Jimeno
B-cell non-Hodgkin's lymphomas are the most common hematological malignancies, which despite improvements in chemo-immunotherapy, carry a uniformly poor prognosis in the relapsed/refractory setting. CD19 is an antigen expressed on the surface of most malignancies arising from the B cells, and adoptive transfer of anti-CD19 chimeric antigen receptor (CAR)-expressing T cells has been shown to be effective in treating these B-cell malignancies. Axicabtagene ciloleucel (axi-cel, KTE-C19) is an autologous anti-CD19 CAR T-cell therapy which has shown high overall response rates and a manageable safety profile in patients with relapsed or refractory B-cell malignancies who lack effective and curative treatment options...
March 2018: Drugs of Today
https://www.readbyqxmd.com/read/29769201/in-vitro-priming-of-adoptively-transferred-t-cells-with-a-ror%C3%AE-agonist-confers-durable-memory-and-stemness-in-vivo
#12
Xiao Hu, Kinga Majchrzak, Xikui Liu, Megan M Wyatt, Chauncey Spooner, Jacques Moisan, Weiping Zou, Laura L Carter, Chrystal M Paulos
Adoptive T cell transfer therapy is an FDA-approved treatment for leukemia that relies on the ex vivo expansion and re-infusion of a patient's immune cells, which can be engineered with a chimeric antigen receptor (CAR) for more efficient tumor recognition. Type 17 T cells, controlled transcriptionally by RORγ, have been reported to mediate potent anti-tumor effects superior to those observed with conventionally expanded T cells. Here we demonstrate that addition of a synthetic, small molecule RORγ agonist during ex vivo expansion potentiates the anti-tumor activity of human Th17 and Tc17 cells redirected with a CAR...
May 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29768737/providence-of-cd25-kir-cd127-foxp3-cd8-t-cell-subset-determines-the-dynamics-of-tumor-immune-surveillance
#13
Sreeparna Chakraborty, Pushpak Bhattacharjee, Abir K Panda, Kirti Kajal, Sayantan Bose, Gaurisankar Sa
CD8+ T-regulatory cells are progressively emerging as crucial components of immune system. The previous report suggests the presence of FOXP3-positive CD8+ Treg cells, similar to CD4+ Tregs, in cancer patients which produce high levels of IL10 and TGFβ for its immunosuppressive activities. At an early stage of tumor development, we have identified a subset of FOXP3-negative CD8+ CD25+ KIR+ CD127- a Treg-like subset which is essentially IFNγ-positive. However, this early induced CD8+ CD25+ CD127- T cell subset certainly distinct from the IFNγ+ CD8+ T-effecter cells...
May 16, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29768210/engineered-tumor-targeted-t-cells-mediate-enhanced-anti-tumor-efficacy-both-directly-and-through-activation-of-the-endogenous-immune-system
#14
Mauro P Avanzi, Oladapo Yeku, Xinghuo Li, Dinali P Wijewarnasuriya, Dayenne G van Leeuwen, Kenneth Cheung, Hyebin Park, Terence J Purdon, Anthony F Daniyan, Matthew H Spitzer, Renier J Brentjens
Chimeric antigen receptor (CAR) T cell therapy has proven clinically beneficial against B cell acute lymphoblastic leukemia and non-Hodgkin's lymphoma. However, suboptimal clinical outcomes have been associated with decreased expansion and persistence of adoptively transferred CAR T cells, antigen-negative relapses, and impairment by an immunosuppressive tumor microenvironment. Improvements in CAR T cell design are required to enhance clinical efficacy, as well as broaden the applicability of this technology...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29761172/loss-of-hypoxia-inducible-factor-1%C3%AE-aggravates-%C3%AE-%C3%AE-t-cell-mediated-inflammation-during-acetaminophen-induced-liver-injury
#15
Tomohiro Suzuki, Shoko Minagawa, Takashi Yamazaki, Takatomo Arai, Mai Kanai, Satoko Shinjo, Nobuhito Goda
Acetaminophen (APAP)-induced liver injury is closely associated with acute hepatic inflammation. Hypoxia-inducible factor-1 (HIF-1) is activated during immunological processes and regulates gene expressions in various types of immune cells. Although HIF-1 controls the differentiation and functions of conventional T cells in chronic inflammation, the pathological importance of HIF-1 in innate-like T cells during acute inflammation remains unknown. Here, we investigated the role of HIF-1 in innate-like γδ T cells during APAP-induced acute liver injury...
May 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29760084/distinct-macrophage-populations-direct-inflammatory-versus-physiological-changes-in-adipose-tissue
#16
David A Hill, Hee-Woong Lim, Yong Hoon Kim, Wesley Y Ho, Yee Hoon Foong, Victoria L Nelson, Hoang C B Nguyen, Kavya Chegireddy, Jihoon Kim, Andreas Habertheuer, Prashanth Vallabhajosyula, Taku Kambayashi, Kyoung-Jae Won, Mitchell A Lazar
Obesity is characterized by an accumulation of macrophages in adipose, some of which form distinct crown-like structures (CLS) around fat cells. While multiple discrete adipose tissue macrophage (ATM) subsets are thought to exist, their respective effects on adipose tissue, and the transcriptional mechanisms that underlie the functional differences between ATM subsets, are not well understood. We report that obese fat tissue of mice and humans contain multiple distinct populations of ATMs with unique tissue distributions, transcriptomes, chromatin landscapes, and functions...
May 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29755697/natural-killer-cells-as-a-therapeutic-tool-for-infectious-diseases-current-status-and-future-perspectives
#17
REVIEW
Stanislaw Schmidt, Lars Tramsen, Bushra Rais, Evelyn Ullrich, Thomas Lehrnbecher
Natural Killer (NK) cells are involved in the host immune response against infections due to viral, bacterial and fungal pathogens, all of which are a significant cause of morbidity and mortality in immunocompromised patients. Since the recovery of the immune system has a major impact on the outcome of an infectious complication, there is major interest in strengthening the host response in immunocompromised patients, either by using cytokines or growth factors or by adoptive cellular therapies transfusing immune cells such as granulocytes or pathogen-specific T-cells...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29755462/comparison-of-phenotypic-and-functional-characteristics-between-canine-non-b-non-t-natural-killer-lymphocytes-and-cd3-cd5-dim-cd21-cytotoxic-large-granular-lymphocytes
#18
Soo-Hyeon Lee, Dong-Jun Shin, Yoseop Kim, Cheol-Jung Kim, Je-Jung Lee, Mee Sun Yoon, Tung Nguyen Thanh Uong, Dohyeon Yu, Ji-Youn Jung, Duck Cho, Bock-Gie Jung, Sang-Ki Kim, Guk-Hyun Suh
Natural killer (NK) cells play a pivotal role in the immune response against infections and malignant transformation, and adopted transfer of NK cells is thought to be a promising therapeutic approach for cancer patients. Previous reports describing the phenotypic features of canine NK cells have produced inconsistent results. Canine NK cells are still defined as non-B and non-T (CD3- CD21- ) large granular lymphocytes. However, a few reports have demonstrated that canine NK cells share the phenotypic characteristics of T lymphocytes, and that CD3+ CD5dim CD21- lymphocytes are putative canine NK cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29755449/immunization-elicits-antigen-specific-antibody-sequestration-in-dorsal-root-ganglia-sensory-neurons
#19
Manojkumar Gunasekaran, Prodyot K Chatterjee, Andrew Shih, Gavin H Imperato, Meghan Addorisio, Gopal Kumar, Annette Lee, John F Graf, Dan Meyer, Michael Marino, Christopher Puleo, Jeffrey Ashe, Maureen A Cox, Tak W Mak, Chad Bouton, Barbara Sherry, Betty Diamond, Ulf Andersson, Thomas R Coleman, Christine N Metz, Kevin J Tracey, Sangeeta S Chavan
The immune and nervous systems are two major organ systems responsible for host defense and memory. Both systems achieve memory and learning that can be retained, retrieved, and utilized for decades. Here, we report the surprising discovery that peripheral sensory neurons of the dorsal root ganglia (DRGs) of immunized mice contain antigen-specific antibodies. Using a combination of rigorous molecular genetic analyses, transgenic mice, and adoptive transfer experiments, we demonstrate that DRGs do not synthesize these antigen-specific antibodies, but rather sequester primarily IgG1 subtype antibodies...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29755412/association-between-progesterone-elevation-on-the-day-of-human-chronic-gonadotropin-trigger-and-pregnancy-outcomes-after-fresh-embryo-transfer-in-in-vitro-fertilization-intracytoplasmic-sperm-injection-cycles
#20
REVIEW
Sandro C Esteves, Gautam Khastgir, Jatin Shah, Kshitiz Murdia, Shweta Mittal Gupta, Durga G Rao, Soumyaroop Dash, Kundan Ingale, Milind Patil, Kunji Moideen, Priti Thakor, Pavitra Dewda
Progesterone elevation (PE) during the late follicular phase of controlled ovarian stimulation in fresh embryo transfer in vitro fertilization (IVF)/intracytoplasmic sperm injection cycles has been claimed to be associated with decreased pregnancy rates. However, the evidence is not unequivocal, and clinicians still have questions about the clinical validity of measuring P levels during the follicular phase of stimulated cycles. We reviewed the existing literature aimed at answering four relevant clinical questions, namely (i) Is gonadotropin type associated with PE during the follicular phase of stimulated cycles? (ii) Is PE on the day of human chorionic gonadotropin (hCG) associated with negative fresh embryo transfer IVF/intracytoplasmic sperm injection (ICSI) cycles outcomes in all patient subgroups? (iii) Which P thresholds are best to identify patients at risk of implantation failure due to PE in a fresh embryo transfer? and (iv) Should a freeze all policy be adopted in all the cycles with PE on the day of hCG? The existing evidence indicates that late follicular phase progesterone rise in gonadotropin releasing analog cycles is mainly caused by the supraphysiological stimulation of granulosa cells with exogenous follicle-stimulating hormone...
2018: Frontiers in Endocrinology
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