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https://www.readbyqxmd.com/read/28108463/targeting-glioblastoma-with-car-t-cells
#1
(no author information available yet)
CAR T cells targeting IL13Rα2 proved effective against recurrent multifocal leptomeningeal glioblastoma, according to a case report. Direct delivery of the therapy into the cerebrospinal fluid was well tolerated, completely eliminating the patient's brain and spinal tumors for 7.5 months, during which the patient resumed his normal activities.
January 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28106050/an-oxygen-sensitive-self-decision-making-engineered-car-t-cell
#2
Alexandre Juillerat, Alan Marechal, Jean Marie Filhol, Yannick Valogne, Julien Valton, Aymeric Duclert, Philippe Duchateau, Laurent Poirot
A key to the success of chimeric antigen receptor (CAR) T-cell based therapies greatly rely on the capacity to identify and target antigens with expression restrained to tumor cells. Here we present a strategy to generate CAR T-cells that are only effective locally (tumor tissue), potentially also increasing the choice of targetable antigens. By fusing an oxygen sensitive subdomain of HIF1α to a CAR scaffold, we generated CAR T-cells that are responsive to a hypoxic environment, a hallmark of certain tumors...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28101795/locally-advanced-pancreatic-cancer-successfully-treated-by-distal-pancreatectomy-with-celiac-axis-resection-dp-car-after-s-1-with-radiation-therapy-followed-by-gemcitabine-nab-paclitaxel-therapy-a-case-report
#3
Kyohei Ariake, Fuyuhiko Motoi, Masamichi Mizuma, Keigo Murakami, Tatsuyuki Takadate, Hideo Ohtsuka, Koji Fukase, Kunihiro Masuda, Hiroki Hayashi, Kei Nakagawa, Naoaki Sakata, Takanori Morikawa, Shimpei Maeda, Takeshi Naitoh, Shinichi Egawa, Michiaki Unno
BACKGROUND: The prognosis for pancreatic cancer remains dismal because many patients are diagnosed with unresectable cancer at the initial diagnosis. Recently, conversion surgery was reported as an effective treatment for initially unresectable pancreatic cancer with a favorable response to non-surgical treatment lasting over 240 days. Here, we describe a case of locally advanced pancreatic cancer (LAPC) successfully resected after treatment with S-1 and radiation followed by gemcitabine/nab-paclitaxel therapy...
December 2017: Surgical Case Reports
https://www.readbyqxmd.com/read/28100832/reporter-gene-imaging-of-targeted-t-cell-immunotherapy-in-recurrent-glioma
#4
Khun Visith Keu, Timothy H Witney, Shahriar Yaghoubi, Jarrett Rosenberg, Anita Kurien, Rachel Magnusson, John Williams, Frezghi Habte, Jamie R Wagner, Stephen Forman, Christine Brown, Martin Allen-Auerbach, Johannes Czernin, Winson Tang, Michael C Jensen, Behnam Badie, Sanjiv S Gambhir
High-grade gliomas are aggressive cancers that often become rapidly fatal. Immunotherapy using CD8(+) cytotoxic T lymphocytes (CTLs), engineered to express both herpes simplex virus type 1 thymidine kinase (HSV1-TK) and interleukin-13 (IL-13) zetakine chimeric antigen receptor (CAR), is a treatment strategy with considerable potential. To optimize this and related immunotherapies, it would be helpful to monitor CTL viability and trafficking to glioma cells. We show that noninvasive positron emission tomography (PET) imaging with 9-[4-[(18)F]fluoro-3-(hydroxymethyl)butyl]guanine ([(18)F]FHBG) can track HSV1-tk reporter gene expression present in CAR-engineered CTLs...
January 18, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28094575/treatment-approaches-of-hard-to-treat-non-hodgkin-lymphomas
#5
Lakshminarayanan Nandagopal, Amitkumar Mehta
Even after recent advancements with monoclonal antibodies, antibody drug conjugates and immune therapies, relapsed and refractory lymphomas remain challenging to treat; and the definition and treatment approaches of hard-to-treat lymphomas (HTL) continue to evolve. Areas covered: In this review, we will address HTL encompassing diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL) and peripheral T cell lymphomas (PTCL). DLBCL, which comprises 30-40% of non-Hodgkin lymphomas is a highly aggressive and heterogeneous malignancy, with primary refractory or relapsed disease remaining a therapeutic challenge...
January 17, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28089834/recent-clinical-trials-utilizing-chimeric-antigen-receptor-t-cells-therapies-against-solid-tumors
#6
Shuanglin Han, Olivier Latchoumanin, Guang Wu, Gang Zhou, Lionel Hebbard, Jacob George, Liang Qiao
Chimeric antigen receptors (CARs) are a series of manufactured receptors that have the capacity of binding to specific antigens expressed on surface of tumor cells. A CAR normally has an extracellular antigen recognition domain derived from single variable chain of a monoclonal antibody, a transmembrane domain and an intracellular T cell activation domain. During the last decade, CAR-T cells were demonstrated to possess great therapeutic effects on hematological malignancies. However, strategies using CAR-T cells to treat solid tumors have been hindered by considerable obstacles including "on tissue off target" effects and cytokine storm syndrome...
January 12, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28088790/intraperitoneal-immunotherapy-with-t-cells-stably-and-transiently-expressing-anti-epcam-car-in-xenograft-models-of-peritoneal-carcinomatosis
#7
Wei Xia Ang, Zhendong Li, Zhixia Chi, Shou-Hui Du, Can Chen, Johan C K Tay, Han Chong Toh, John E Connolly, Xue Hu Xu, Shu Wang
The epithelial cell adhesion molecule (EpCAM) is overexpressed in a wide variety of tumor types, including peritoneal carcinomatosis (PC) from gastrointestinal and gynecological malignancies. To develop a chimeric antigen receptor T (CART) cell therapy approach to treat patients with end-stage PC, we constructed third generation CARs specific to EpCAM using the 4D5MOC-B single chain variable fragment. CART cells were generated with lentiviral transduction and exhibited specific in vitro killing activity against EpCAM-positive human ovarian and colorectal cancer cells...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28087203/the-use-of-modified-ride-on-cars-to-maximize-mobility-and-improve-socialization-a-group-design
#8
Hsiang-Han Huang, Chia-Ling Chen
AIM: To examine the effects of ride-on car (ROC) training versus conventional therapy on mobility and social function in young children with disabilities in a hospital-based environment. METHODS AND PROCEDURES: Twenty young children with disabilities, aged 1-3 years, were recruited. The treatment group (n=10) received ROC training of 2h/session, 2 sessions/week for a total of 9 weeks in the hospital environment. The control group (n=10) received conventional therapy alone...
January 10, 2017: Research in Developmental Disabilities
https://www.readbyqxmd.com/read/28079265/chimeric-antigen-receptor-t-cells-in-hematologic-malignancies
#9
Brandon R Shank, Bryan Do, Adrienne Sevin, Sheree E Chen, Sattva S Neelapu, Sandra B Horowitz
Patients with B cell hematologic malignancies who progress through first or second line chemotherapy have a poor prognosis. Early clinical trials with autologous anti-CD19 chimeric antigen receptor (CAR) T cells have demonstrated promising results for patients who have relapsed or refractory disease. Lymphodepleting conditioning regimens including cyclophosphamide, fludarabine, pentostatin, bendamustine, interleukin-2, and total body irradiation are often administered prior to infusion of CAR T cells, allowing for greater T cell expansion...
January 12, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28071584/major-highlights-of-the-car-tcr-summit-boston-2016
#10
Vita Golubovskaya, Robert Berahovich, Shirley Xu, Hizkia Harto, Lijun Wu
Cellular immunotherapies such as CAR-T cell therapy and TCR-T cell therapy are relatively new, highly promising approaches for the treatment of cancer. In CAR-T cell therapy, a patient's T cells are engineered to express chimeric antigen receptors targeting tumor-associated cell surface antigens. In TCR-T cell therapy, the patient's T cells are engineered to express receptors targeting intracellular antigens. This report will summarize presentations from the recent CAR-TCR summit in Boston on September 13-16, 2016...
10, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28070245/horizontally-root-fractured-teeth-with-pulpal-vitality-two-case-reports
#11
Luciano Silva, Pâmella Álvares, José Alcides Arruda, Leni Verônica Silva, Cleomar Rodrigues, Ana Paula Veras Sobral, Marcia Silveira
This case study reports the successful outcome of horizontal root fractures of two different patients, which took place in permanent incisors. Report 1 describes a case of a 29-year-old patient who suffered a mandibular trauma affecting mainly the lower central incisors, caused by a car accident. A panoramic radiograph was taken right after the accident and showed a horizontal root fracture in the middle third of tooth 42, which went untreated. Report 2 illustrates a case of a 17-year-old male patient who searched for orthodontic therapy and the periapical radiograph showed horizontal root fracture in tooth 11 caused by a previous trauma, which went untreated as well...
December 28, 2016: World Journal of Radiology
https://www.readbyqxmd.com/read/28069570/anti-cd22-car-therapy-leads-to-all-remissions
#12
(no author information available yet)
In a first-in-human trial of an anti-CD22 chimeric antigen receptor T-cell therapy in children and young adults with relapsed and refractory acute lymphocytic leukemia, researchers found that the immunotherapeutic approach was not only feasible and safe, but also effective, leading to remissions in most patients. Infusions of higher numbers of T cells correlated with improved responses.
January 9, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28068367/cell-surface-integrins-and-car-are-both-essential-for-adenovirus-type-5-transduction-of-canine-cells-of-lymphocytic-origin
#13
Payal Agarwal, Elizabeth A Gammon, Abdul Mohin Sajib, Maninder Sandey, Bruce F Smith
Adenoviruses are the most widely used vectors in cancer gene therapy. Adenoviruses vectors are well characterized and are easily manipulated. Adenovirus serotype 5 (Ad5) is the most commonly used human serotype. Ad5 internalization into host cells is a combined effect of binding of Ad5 fiber knob with the coxsackie virus and adenovirus receptor (CAR) and binding of RGD motifs in viral penton to cell surface integrins (αvβ3, αvβ5). Ad5's wide range of host-cell transduction and lack of integration into the host genome have made it an excellent choice for cancer therapeutics...
2017: PloS One
https://www.readbyqxmd.com/read/28067900/donor-cd19-car-t-cells-exert-potent-graft-versus-lymphoma-activity-with-diminished-graft-versus-host-activity
#14
Arnab Ghosh, Melody Smith, Scott E James, Marco L Davila, Enrico Velardi, Kimon V Argyropoulos, Gertrude Gunset, Fabiana Perna, Fabiana M Kreines, Emily R Levy, Sophie Lieberman, Hillary V Jay, Andrea Z Tuckett, Johannes L Zakrzewski, Lisa Tan, Lauren F Young, Kate Takvorian, Jarrod A Dudakov, Robert R Jenq, Alan M Hanash, Ana Carolina F Motta, George F Murphy, Chen Liu, Andrea Schietinger, Michel Sadelain, Marcel R M van den Brink
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematological malignancies. However, graft-versus-host disease (GVHD) and relapse after allo-HSCT remain major impediments to the success of allo-HSCT. Chimeric antigen receptors (CARs) direct tumor cell recognition of adoptively transferred T cells. CD19 is an attractive CAR target, which is expressed in most B cell malignancies, as well as in healthy B cells. Clinical trials using autologous CD19-targeted T cells have shown remarkable promise in various B cell malignancies...
January 9, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28067588/health-benefits-of-fiber-fermentation
#15
Wendy J Dahl, Nicole C Agro, Åsa M Eliasson, Kaley L Mialki, Joseph D Olivera, Carley T Rusch, Carly N Young
Although fiber is well recognized for its effect on laxation, increasing evidence supports the role of fiber in the prevention and treatment of chronic disease. The aim of this review is to provide an overview of the health benefits of fiber and its fermentation, and describe how the products of fermentation may influence disease risk and treatment. Higher fiber intakes are associated with decreased risk of cardiovascular disease, type 2 diabetes, and some forms of cancer. Fiber may also have a role in lowering blood pressure and in preventing obesity by limiting weight gain...
January 9, 2017: Journal of the American College of Nutrition
https://www.readbyqxmd.com/read/28067179/cd20-based-immunotherapy-of-b-cell-derived-hematologic-malignancies
#16
Dariush Shanehbandi, Jafar Majidi, Tohid Kazemi, Behzad Baradaran, Leili Aghebati-Maleki
CD20 is a surface antigen which is expressed at certain stages of B-cell differentiation. Targeting the CD20-positive B-cells with therapeutic monoclonal antibodies (MAbs) has been an effectual strategy in the treatment of hematologic malignancies such as non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Initial success with Rituximab (RTX) has encouraged the creation and development of more effective CD20 based therapeutics. However, treatment with conventional MAbs has not been adequate to overcome the problems such as refractory/relapsed disease...
January 9, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28067102/preoperative-modifiable-risk-factors-in-colorectal-surgery-an-observational-cohort-study-identifying-the-possible-value-of-prehabilitation
#17
Stefanus van Rooijen, Francesco Carli, Susanne O Dalton, Christoffer Johansen, Jeanne Dieleman, Rudi Roumen, Gerrit Slooter
BACKGROUND: Colorectal cancer (CRC) is the second most prevalent type of cancer in the world. Surgery is the most common therapeutic intervention, and associated with 20-40% reduction in physiological and functional capacity. Postoperative complications occur in up to 50% of patients resulting in higher mortality rates and greater hospital costs. The number and severity of complications is closely related to patients' preoperative performance status. The aim of this study was to identify the most important preoperative modifiable risk factors that could be part of a multimodal prehabilitation program...
January 9, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28067101/promoting-a-culture-of-prehabilitation-for-the-surgical-cancer-patient
#18
Francesco Carli, Chelsia Gillis, Celena Scheede-Bergdahl
BACKGROUND: Traditional rehabilitative approaches to perioperative cancer care have focused on the postoperative period to facilitate the return to presurgical baseline conditions. However, there is some realization that the preoperative period can be a very effective time for intervention as the patients are more amenable to target their physiological condition to prepare to overcome the metabolic cost of the surgical stress. METHODS: We undertook a narrative review of the current literature on surgical prehabilitation and discussed the current evidence of preoperative interventions before cancer surgery in order to increase physiological reserve before surgery and accelerate postoperative recovery...
January 9, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28064157/fviii-specific-human-chimeric-antigen-receptor-car-t-regulatory-cells-suppress-t-and-b-cell-responses-to-fviii
#19
Jeongheon Yoon, Anja Schmidt, Ai-Hong Zhang, Christoph Königs, Yong Chan Kim, David W Scott
Replacement therapy with factor VIII (FVIII) is used in hemophilia A patients for treatment of bleeding episodes or for prophylaxis. A common and serious problem with this therapy is the patient's immune response to FVIII, due to a lack of tolerance, leading to the formation of inhibitory antibodies. Development of tolerogenic therapies, other than standard ITI, is an unmet goal. We previously generated engineered antigen- specific regulatory T cells (Tregs), created by transduction of a recombinant T cell receptor (TCR) isolated from a hemophilia A subject's T cell clone...
November 15, 2016: Blood
https://www.readbyqxmd.com/read/28059624/pre-clinical-development-of-gene-modification-of-hematopoietic-stem-cells-with-chimeric-antigen-receptors-for-cancer-immunotherapy
#20
Sarah M Larson, Laurel C Truscott, Tzu-Ting Chiou, Amie Patel, Roy Kao, Andy Tu, Tulika Tyagi, Xiang Lu, David Elashoff, Satiro N De Oliveira
Patients with refractory or recurrent B-lineage hematologic malignancies have less than 50% of chance of cure despite intensive therapy and innovative approaches are needed. We hypothesize that gene modification of hematopoietic stem cells (HSC) with an anti-CD19 chimeric antigen receptor (CAR) will produce a multi-lineage, persistent immunotherapy against B-lineage malignancies that can be controlled by the HSVsr39TK suicide gene. High-titer third-generation self-inactivating lentiviral constructs were developed to deliver a second-generation CD19-specific CAR and the herpes simplex virus thymidine kinase HSVsr39TK to provide a suicide gene to allow ablation of gene-modified cells if necessary...
January 6, 2017: Human Vaccines & Immunotherapeutics
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