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CAR T therapy

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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/28100832/reporter-gene-imaging-of-targeted-t-cell-immunotherapy-in-recurrent-glioma
#3
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
#4
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
#5
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
#6
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/28079265/chimeric-antigen-receptor-t-cells-in-hematologic-malignancies
#7
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
#8
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/28069570/anti-cd22-car-therapy-leads-to-all-remissions
#9
(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/28067900/donor-cd19-car-t-cells-exert-potent-graft-versus-lymphoma-activity-with-diminished-graft-versus-host-activity
#10
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
#11
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
#12
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/28064157/fviii-specific-human-chimeric-antigen-receptor-car-t-regulatory-cells-suppress-t-and-b-cell-responses-to-fviii
#13
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/28053197/chimeric-antigen-receptor-t-cells-therapy-for-tumor-immunotherapy
#14
Huanhuan Sha, Dandan Wang, Dali Yan, Yong Hu, Sujin Lang, Siwen Liu, Jifeng Feng
Chimeric antigen receptor (CAR) T cells therapies, as one of the cancer immunotherapies, have heralded a new era of treating cancer. The accumulating data, especially about CAR modified T cells against CD19 support that CAR-T cells therapy is a highly effective immune therapy for B-cell malignancies. Apart from CD19, there have been many trials of CAR T cells directed other tumor specific or associated antigens (TSAs/TAAs) in hematologic malignancies and solid tumors. This review will briefly summarize basic CAR structure, parts of reported TSAs/TAAs, results of the clinical trials of CAR-T cells therapies as well as two life-threatening side effects...
January 4, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28050977/influence-of-age-on-factors-associated-with-peri-implant-bone-loss-after-prosthetic-rehabilitation-over-osseointegrated-implants
#15
Rejane El Pedro, João P De Carli, Maria Ss Linden, Igor Fp Lima, Luiz R Paranhos, Max D Costa, Ângelo Jg Bós
INTRODUCTION: To verify the influence of age on factors associated with peri-implant bone loss after prosthetic rehabilitation over osseointegrated implants. MATERIALS AND METHODS: This is an analytical, observational, and longitudinal study with initial 23 participants. Patients presenting with osseointegrated implants with their respective prostheses installed were included, and they could be carriers of chronic and degenerative diseases, such as diabetes, osteoporosis, hypothyroidism, cardiovascular disease (CVD), and systemic arterial hypertension...
January 1, 2017: Journal of Contemporary Dental Practice
https://www.readbyqxmd.com/read/28049484/a-new-insight-in-chimeric-antigen-receptor-engineered-t-cells-for-cancer-immunotherapy
#16
REVIEW
Erhao Zhang, Hanmei Xu
Adoptive cell therapy using chimeric antigen receptor (CAR)-engineered T cells has emerged as a very promising approach to combating cancer. Despite its ability to eliminate tumors shown in some clinical trials, CAR-T cell therapy involves some significant safety challenges, such as cytokine release syndrome (CRS) and "on-target, off-tumor" toxicity, which is related to poor control of the dose, location, and timing of T cell activity. In the past few years, some strategies to avoid the side effects of CAR-T cell therapy have been reported, including suicide gene, inhibitory CAR, dual-antigen receptor, and the use of exogenous molecules as switches to control the CAR-T cell functions...
January 3, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28029927/regression-of-glioblastoma-after-chimeric-antigen-receptor-t-cell-therapy
#17
Christine E Brown, Darya Alizadeh, Renate Starr, Lihong Weng, Jamie R Wagner, Araceli Naranjo, Julie R Ostberg, M Suzette Blanchard, Julie Kilpatrick, Jennifer Simpson, Anita Kurien, Saul J Priceman, Xiuli Wang, Todd L Harshbarger, Massimo D'Apuzzo, Julie A Ressler, Michael C Jensen, Michael E Barish, Mike Chen, Jana Portnow, Stephen J Forman, Behnam Badie
A patient with recurrent multifocal glioblastoma received chimeric antigen receptor (CAR)-engineered T cells targeting the tumor-associated antigen interleukin-13 receptor alpha 2 (IL13Rα2). Multiple infusions of CAR T cells were administered over 220 days through two intracranial delivery routes - infusions into the resected tumor cavity followed by infusions into the ventricular system. Intracranial infusions of IL13Rα2-targeted CAR T cells were not associated with any toxic effects of grade 3 or higher...
29, 2016: New England Journal of Medicine
https://www.readbyqxmd.com/read/28028314/redirecting-t-cells-to-eradicate-b-cell-acute-lymphoblastic-leukemia-bispecific-t-cell-engagers-and-chimeric-antigen-receptors
#18
REVIEW
I Aldoss, R C Bargou, D Nagorsen, G R Friberg, P A Baeuerle, S J Forman
Recent advances in antibody technology to harness T-cells for cancer immunotherapy, particularly in the difficult-to-treat setting of relapsed or refractory acute lymphoblastic leukemia (r/r ALL), has led to innovative methods for directing cytotoxic T-cells to specific surface antigens on cancer cells. One approach involves administration of soluble bispecific (or dual-affinity) antibody-based constructs that temporarily bridge T-cells and cancer cells. Another approach infuses ex vivo-engineered T-cells that express a surface plasma membrane-inserted antibody construct called a chimeric antigen receptor (CAR)...
December 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28027623/expression-of-a-chimeric-antigen-receptor-specific-for-donor-hla-class-i-enhances-the-potency-of-human-regulatory-t-cells-in-preventing-human-skin-transplant-rejection
#19
Dominic A Boardman, Christina Philippeos, Gilbert O Fruhwirth, Mohammad A A Ibrahim, Rosalind F Hannen, Dianne Cooper, Federica M Marelli-Berg, Fiona M Watt, Robert I Lechler, John Maher, Lesley A Smyth, Giovanna Lombardi
Regulatory T cell (Treg) therapy using recipient-derived Tregs expanded ex vivo is currently being investigated clinically by us and others as a means of reducing allograft rejection following organ transplantation. Data from animal models has demonstrated that adoptive transfer of allospecific Tregs offers greater protection from graft rejection compared to polyclonal Tregs. Chimeric antigen receptors (CAR) are clinically-translatable synthetic fusion proteins which can redirect the specificity of T cells towards designated antigens...
December 27, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/28025979/driving-gene-engineered-t-cell-immunotherapy-of-cancer
#20
REVIEW
Laura A Johnson, Carl H June
Chimeric antigen receptor (CAR) gene-engineered T cell therapy holds the potential to make a meaningful difference in the lives of patients with terminal cancers. For decades, cancer therapy was based on biophysical parameters, with surgical resection to debulk, followed by radiation and chemotherapy to target the rapidly growing tumor cells, while mostly sparing quiescent normal tissues. One breakthrough occurred with allogeneic bone-marrow transplant for patients with leukemia, which provided a sometimes curative therapy...
January 2017: Cell Research
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