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https://www.readbyqxmd.com/read/28729550/anti-tumor-activity-and-immunotherapeutic-potential-of-a-bisphosphonate-prodrug
#1
Yoshimasa Tanaka, Masashi Iwasaki, Kaoru Murata-Hirai, Kenji Matsumoto, Kosuke Hayashi, Haruki Okamura, Tomoharu Sugie, Nagahiro Minato, Craig T Morita, Masakazu Toi
Bisphosphonates have benefits in breast cancer and multiple myeloma patients and have been used with adoptive immunotherapy with γδ T cells expressing Vγ2 Vδ2 TCRs. Although treatment with γδ T cells is safe, it has shown limited efficacy. Present bisphosphonates stimulate γδ T cells but were designed to inhibit bone resorption rather than treating cancer and have limited oral absorption, tumor cell entry, and cause bone side effects. The development of phosphate and phosphonate nucleotide prodrugs has led to important drugs for hepatitis C and HIV...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28728493/treating-breast-cancer-with-cell-based-approaches-an-overview
#2
Susanna Gallo, Dario Sangiolo, Fabrizio Carnevale Schianca, Massimo Aglietta, Filippo Montemurro
Breast cancer is the most common malignancy in women. Despite there being considerable progress in the treatment of this disease, metastatic dissemination is still considered an incurable condition at the present time, causing 500,000 deaths worldwide every year. Although most of the research efforts have been focused on pharmacological approaches, over the last three decades, the use of bone marrow and peripheral blood-derived cell therapy approaches have been attempted and developed. Areas covered: This review will briefly address cell therapy for breast cancer, including autologous stem cell transplantations for overcoming the myelosuppressive effects of high-dose chemotherapy, allogeneic stem cell transplants and adoptive immunotherapy using bone-marrow derived T-cells...
July 20, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28727137/national-evaluation-of-multidisciplinary-quality-metrics-for-head-and-neck-cancer
#3
John D Cramer, Sedona E Speedy, Robert L Ferris, Alfred W Rademaker, Urjeet A Patel, Sandeep Samant
BACKGROUND: The National Quality Forum has endorsed quality-improvement measures for multiple cancer types that are being developed into actionable tools to improve cancer care. No nationally endorsed quality metrics currently exist for head and neck cancer. METHODS: The authors identified patients with surgically treated, invasive, head and neck squamous cell carcinoma in the National Cancer Data Base from 2004 to 2014 and compared the rate of adherence to 5 different quality metrics and whether compliance with these quality metrics impacted overall survival...
July 20, 2017: Cancer
https://www.readbyqxmd.com/read/28724801/tcr-ligand-dissociation-rate-is-a-robust-and-stable-biomarker-of-cd8-t-cell-potency
#4
Mathilde Allard, Barbara Couturaud, Laura Carretero-Iglesia, Minh Ngoc Duong, Julien Schmidt, Gwennaëlle C Monnot, Pedro Romero, Daniel E Speiser, Michael Hebeisen, Nathalie Rufer
Despite influencing many aspects of T cell biology, the kinetics of T cell receptor (TCR) binding to peptide-major histocompatibility molecules (pMHC) remain infrequently determined in patient monitoring or for adoptive T cell therapy. Using specifically designed reversible fluorescent pMHC multimeric complexes, we performed a comprehensive study of TCR-pMHC off-rates combined with various functional assays on large libraries of self/tumor- and virus-specific CD8+ T cell clones from melanoma patients and healthy donors...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28716899/hdac1-upregulation-by-nanog-promotes-multidrug-resistance-and-a-stem-like-phenotype-in-immune-edited-tumor-cells
#5
Kwon-Ho Song, Chel Hun Choi, Hyo-Jung Lee, Se Jin Oh, Seon Rang Woo, Soon-Oh Hong, Kyung Hee Noh, Hanbyoul Cho, Eun Joo Chung, Jae-Hoon Kim, Joon-Yong Chung, Stephen M Hewitt, Seungki Baek, Kyung-Mi Lee, Cassian Yee, Minjoo Son, Chih-Ping Mao, T-C Wu, Tae Woo Kim
Cancer immunoediting drives the adaptation of tumor cells to host immune surveillance. Immunoediting driven by antigen (Ag)-specific T cells enriches NANOG expression in tumor cells, resulting in a stem-like phenotype and immune resistance. Here we identify HDAC1 as a key mediator of the NANOG-associated phenotype. NANOG upregulated HDAC1 through promoter occupancy, thereby decreasing histone H3 acetylation on K14 and K27. NANOG-dependent, HDAC1-driven epigenetic silencing of cell cycle inhibitor CDKN2D and CDKN1B induced stem-like features...
July 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28713896/an-optimized-gene-transfection-system-in-weri-rb1-cells
#6
Ying Liu, Zhigang Fan, Kang Li, Fei Deng, Yunfan Xiong, Meixin Liang, Jian Ge
The pathogenesis of Rb1 gene inactivation indicates that gene therapy could be a promising treatment for retinoblastoma. An appropriate gene transfer system is the basis for successful gene therapy; however, little attention has been given to an effective gene transfer system for retinoblastoma therapy in previous studies. This study was designed to provide an optimized transgene system for WERI‑Rb1 cells (W-RBCs). Green fluorescent protein (GFP) was adopted as a reporter. Four classic viral vectors based on retroviruses, recombinant adeno-associated viruses (rAAV2, rAAV2/1), lentiviruses (LVs) and a novel non-viral vector X-treme HP reagent were adopted for W-RBC gene transfection...
July 6, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28713676/immunotherapy-for-malignant-pleural-mesothelioma-current-status-and-future-directions
#7
REVIEW
Jordan Dozier, Hua Zheng, Prasad S Adusumilli
Malignant pleural mesothelioma (MPM) has been marked historically by poor prognosis. Current standard of care for this deadly disease results in sub-optimal improvements in overall survival (OS), which has prompted researchers to explore innovative treatment alternatives. Immunotherapy is an emerging therapeutic modality that harnesses the power of the human immune system. In this review, we summarize the different methods of immunotherapy for malignant pleural mesothelioma. Using ClinicalTrials.gov we searched the terms "immunotherapy" and "immune therapy" combined with "pleural mesothelioma"...
June 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28713379/op9-feeder-cells-are-superior-to-m2-10b4-cells-for-the-generation-of-mature-and-functional-natural-killer-cells-from-umbilical-cord-hematopoietic-progenitors
#8
Lara Herrera, Juan Manuel Salcedo, Silvia Santos, Miguel Ángel Vesga, Francisco Borrego, Cristina Eguizabal
Adoptive natural killer (NK) cell therapy relies on the acquisition of large numbers of mature and functional NK cells. An option for future immunotherapy treatments is to use large amounts of NK cells derived and differentiated from umbilical cord blood (UCB) CD34(+) hematopoietic stem cells (HSCs), mainly because UCB is one of the most accessible HSC sources. In our study, we compared the potential of two stromal cell lines, OP9 and M2-10B4, for in vitro generation of mature and functional CD56(+) NK cells from UCB CD34(+) HSC...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28712863/harnessing-the-cd1-restricted-t-cell-response-for-leukemia-adoptive-immunotherapy
#9
Michela Consonni, Claudia de Lalla, Alessandra Bigi, Paolo Dellabona, Giulia Casorati
Disease recurrence following chemotherapy and allogeneic hematopoietic cell transplantation is the major unmet clinical need of acute leukemia. Adoptive cell therapy (ACT) with allogeneic T lymphocytes can control recurrences at the cost of inducing detrimental GVHD. Targeting T cell recognition on leukemia cells is therefore needed to overcome the problem and ensure safe and durable disease remission. In this review, we discuss adoptive cells therapy based on CD1-restricted T cells specific for tumor associated self-lipid antigens...
July 8, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28711285/anti-il-21-monoclonal-antibody-combined-with-liraglutide-effectively-reverses-established-hyperglycemia-in-mouse-models-of-type-1-diabetes
#10
Anna K Rydén, Nikole R Perdue, Philippe P Pagni, Claire B Gibson, Sowbarnika S Ratliff, Rikke K Kirk, Travis J Friesen, Claus Haase, Ken Coppieters, Matthias G von Herrath, Tamar E Boursalian
Immunotherapy for type 1 diabetes (T1D) has previously focused on suppressing the autoimmune response against pancreatic beta cells to preserve endogenous insulin production and regulate glucose levels. With increased attention toward combination therapy strategies, studies indicate the multifunctional cytokine interleukin-21 (IL-21) may be a suitable target as an immuno-modulatory arm, while glucagon-like peptide-1 receptor (GLP-1R) agonists may be appropriate as a beta cell protective arm in combination therapy for T1D...
July 12, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28708956/the-power-of-combining-adoptive-cell-therapy-act-and-pathogen-boosted-vaccination-to-treat-solid-tumors
#11
Ryan Zander, Weiguo Cui
Recent advancements in adoptive cell therapy (ACT) are opening up new frontiers for cancer immunotherapy. CAR T cells targeting CD19 have emerged as a remarkable T cell-based therapy for the successful treatment of certain types of leukemia and lymphomas. Despite these clinical successes, as well as significant breakthroughs in T cell engineering, the treatment of solid tumors with ACT remains a relentless challenge. Thus, the current consensus of the field is that an urgent need exists for the design of innovative approaches that can improve the efficacy of ACT in treating solid cancers while maintaining a high degree of reliability and safety...
July 14, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28708802/characterization-and-expansion-of-autologous-gmp-ready-regulatory-t-cells-for-treg-based-cell-therapy-in-patients-with-ulcerative-colitis
#12
Caroline J Voskens, Anika Fischer, Susanne Roessner, Carmen Lorenz, Simon Hirschmann, Raja Atreya, Clemens Neufert, Imke Atreya, Markus F Neurath, Gerold Schuler
BACKGROUND: A local imbalance between regulatory (Treg) and effector T cells is believed to play a major role in gut-specific inflammation, including ulcerative colitis (UC). Restoration of this balance through an adoptive Treg transfer is an attractive new treatment approach in patients who are refractory to current standard therapies. It was our goal to develop a Good Manufacturing Practices (GMP)-conform protocol for expansion of UC Treg cells as a rational backbone for future studies on Treg therapy in UC...
August 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28704709/protective-role-of-surface-toll-like-receptor-9-expressing-neutrophils-in-local-inflammation-during-systemic-inflammatory-response-syndrome-in-mice
#13
Xiuping Meng, Wei Sun, Yunjia Ren, Yue Xiao, Peiyan Zhao, Wenting Lu, Li Hua, Luowei Wang, Liying Wang, Yongli Yu
Clinically, systemic inflammatory response syndrome (SIRS) occurs after serious trauma or sepsis. In sepsis, neutrophils are the major effector cells responsible for eliminating pathogens. However, the role of neutrophils in development of SIRS, especially in local inflammatory area, is controversial. In this study, we established a SIRS mouse model characterized with cytokine-mediated lethal shock by intraperitoneal injection of oligodexynucleotides containing CpG motifs (CpG ODN) in D-galactosamine (D-GalN) sensitized mice based on our previous work and found that abundant neutrophils were rapidly recruited into the peritoneal cavity, where some neutrophils expressed surface TLR9 (sTLR9), defined as sTLR9(+) neutrophils...
July 10, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28702985/photobiomodulation-with-polarized-light-in-the-treatment-of-cutaneous-and-mucosal-ulcerative-lesions
#14
S E Aragona, F R Grassi, G Nardi, J Lotti, G Mereghetti, E Canavesi, E Equizi, A M Puccio, G Gianazza, T Lotti, I Morisi
In recent decades, regenerative medicine has achieved an important evolution at both a conceptual level and scientific production, which explains the current and future possibilities of therapy and daily clinical practice. The main aim of regenerative medicine is the complex system of repair/regeneration. The current literature on the subject demonstrates the advantage of visible light therapy for skin injuries and diseases with the photobiomodulation in which light at low energy levels modulates intra- and extra-cellular photoreceptors by molecular and cellular processes that can stimulate both anti-inflammatory mechanisms and cell proliferative response...
July 13, 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28702462/adoptive-cell-therapy-of-induced-regulatory-t-cells-expanded-by-tolerogenic-dendritic-cells-on-murine-autoimmune-arthritis
#15
Jie Yang, Lidong Liu, Yiming Yang, Ning Kong, Xueyu Jiang, Juan Sun, Rufeng Xie
OBJECTIVE: Tolerogenic dendritic cells (tDCs) can expand TGF-β-induced regulatory T cells (iTregs); however, the therapeutic utility of these expanded iTregs in autoimmune diseases remains unknown. We sought to determine the properties of iTregs expanded by mature tolerogenic dendritic cells (iTregmtDC) in vitro and explore their potential to ameliorate collagen-induced arthritis (CIA) in a mouse model. METHODS: After induction by TGF-β and expansion by mature tDCs (mtDCs), the phenotype and proliferation of iTregmtDC were assessed by flow cytometry...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28700495/immune-recovery-of-middle-aged-hiv-patients-following-antiretroviral-therapy-an-observational-cohort-study
#16
Ngai Sze Wong, Kenny Chi Wai Chan, Edward Ka Hin Cheung, Ka Hing Wong, Shui Shan Lee
In HIV-infected persons, age is negatively associated with optimal CD4 recovery following antiretroviral therapy. Our understanding of the situation in older adults, especially the middle-aged is, however, limited. We undertook to examine the latter's pattern of CD4/CD8 recovery following antiretroviral therapy.Retrospective clinical cohort data of HIV patients diagnosed between 1985 and 2014 in Hong Kong were collected. They were categorized by age at treatment initiation, viz., young adults (age 18-49), middle-aged (age 50-64), and elderly (≥65 years' old)...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28699537/recent-advances-in-polymeric-nanosystems-for-treating-cutaneous-melanoma-and-its-metastasis
#17
Yi-Ping Chou, Yin-Ku Lin, Chun-Han Chen, Jia-You Fang
Melanoma shows a high possibility of mortality after it metastasizes because of its aggressive nature. Although there are several options for anti-melanoma therapy, this skin malignancy is resistant to some therapies. Chemotherapy, biochemotherapy, immunotherapy, and adoptive cell therapy have failed to exhibit a significant amelioration in overall survival. Nanomedicine provides an opportunity to improve the efficiency of the anti-melanoma regimen. Nanoparticles for treating melanoma provide the advantages over conventional therapies such as drug solubility increment, drug stability enhancement, epithelium permeability and bioavailability amelioration, half-life prolonging, tumor targeting, and side effect minimization...
July 10, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28699110/immune-selection-during-tumor-checkpoint-inhibition-therapy-paves-way-for-nk-cell-missing-self-recognition
#18
REVIEW
Karl-Johan Malmberg, Ebba Sohlberg, Jodie P Goodridge, Hans-Gustaf Ljunggren
The ability of NK cells to specifically recognize cells lacking expression of self-MHC class I molecules was discovered over 30 years ago. It provided the foundation for the "missing self" hypothesis. Research in the two past decades has contributed to a detailed understanding of the molecular mechanisms that determine the specificity and strength of NK cell-mediated "missing self" responses to tumor cells. However, in light of the recent remarkable breakthroughs in clinical cancer immunotherapy, the cytolytic potential of NK cells still remains largely untapped in clinical settings...
July 11, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28697053/postoperative-adjuvant-therapy-for-resectable-pancreatic-cancer-with-gemcitabine-and-adoptive-immunotherapy
#19
Hiroto Matsui, Shoichi Hazama, Kazuhiko Sakamoto, Yoshitaro Shindo, Shinsuke Kanekiyo, Masao Nakashima, Satoshi Matsukuma, Yoshihiro Tokuhisa, Michihisa Iida, Nobuaki Suzuki, Kiyoshi Yoshimura, Shigeru Takeda, Tomio Ueno, Shigefumi Yoshino, Masaaki Oka, Hiroaki Nagano
OBJECTIVES: We previously described adoptive immunotherapy (AIT) with cytotoxic T lymphocytes (CTLs) stimulated by the mucin 1 (MUC1)-expressing human pancreatic cancer cell line YPK-1 (MUC1-CTLs) and demonstrated that MUC1-CTLs might prevent liver metastasis. In the present study, we combined gemcitabine (GEM) and AIT for the treatment of pancreatic cancer. METHODS: A total of 43 patients who underwent radical pancreatectomy received treatment with MUC1-CTLs and GEM...
July 11, 2017: Pancreas
https://www.readbyqxmd.com/read/28695922/erratum-tracking-the-t-cell-repertoire-after-adoptive-therapy
#20
Thomas S Watkins, John J Miles
[This corrects the article DOI: 10.1038/cti.2017.16.].
May 2017: Clinical & Translational Immunology
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