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Chimeric antigen therapy

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https://www.readbyqxmd.com/read/28088790/intraperitoneal-immunotherapy-with-t-cells-stably-and-transiently-expressing-anti-epcam-car-in-xenograft-models-of-peritoneal-carcinomatosis
#1
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
#2
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
#3
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
#4
(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
#5
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/28067179/cd20-based-immunotherapy-of-b-cell-derived-hematologic-malignancies
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/28057014/cocktail-treatment-with-egfr-specific-and-cd133-specific-chimeric-antigen-receptor-modified-t-cells-in-a-patient-with-advanced-cholangiocarcinoma
#9
Kai-Chao Feng, Ye-Lei Guo, Yang Liu, Han-Ren Dai, Yao Wang, Hai-Yan Lv, Jian-Hua Huang, Qing-Ming Yang, Wei-Dong Han
BACKGROUND: Cholangiocarcinoma (CCA) is one of the most fatal malignant tumors with increasing incidence, mortality, and insensitivity to traditional chemo-radiotherapy and targeted therapy. Chimeric antigen receptor-modified T cell (CART) immunotherapy represents a novel strategy for the management of many malignancies. However, the potential of CART therapy in treating advanced unresectable/metastatic CCA is uncharted so far. CASE PRESENTATION: In this case, a 52-year-old female who was diagnosed as advanced unresectable/metastatic CCA and resistant to the following chemotherapy and radiotherapy was treated with CART cocktail immunotherapy, which was composed of successive infusions of CART cells targeting epidermal growth factor receptor (EGFR) and CD133, respectively...
January 5, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28053197/chimeric-antigen-receptor-t-cells-therapy-for-tumor-immunotherapy
#10
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/28053195/tcr-based-therapy-for-multiple-myeloma-and-other-b-cell-malignancies-targeting-intracellular-transcription-factor-bob1
#11
Lorenz Jahn, Pleun Hombrink, Renate S Hagedoorn, Michel G D Kester, Dirk M van der Steen, Tania Rodriguez, Tsvetelina Pentcheva-Hoang, Arnoud H de Ru, Marjolein P Schoonakker, Miranda H Meeuwsen, Marieke Griffioen, Peter A van Veelen, J H Frederik Falkenburg, Mirjam H M Heemskerk
Immunotherapy of hematological malignancies or solid tumors by administration of monoclonal antibodies or T-cells engineered to express chimeric antigen receptors or T-cell receptors (TCRs) has demonstrated clinical efficacy. However, antigen-loss tumor escape variants and the absence of currently targeted antigens on several malignancies hampers the widespread application of immunotherapy. We have isolated a TCR targeting a peptide of the intracellular B-cell specific transcription factor BOB1 presented in the context of HLA-B*07:02...
January 4, 2017: Blood
https://www.readbyqxmd.com/read/28049484/a-new-insight-in-chimeric-antigen-receptor-engineered-t-cells-for-cancer-immunotherapy
#12
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
#13
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
#14
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
#15
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
#16
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
https://www.readbyqxmd.com/read/28025978/immune-targets-and-neoantigens-for-cancer-immunotherapy-and-precision-medicine
#17
REVIEW
Rong-Fu Wang, Helen Y Wang
Harnessing the immune system to eradicate malignant cells is becoming a most powerful new approach to cancer therapy. FDA approval of the immunotherapy-based drugs, sipuleucel-T (Provenge), ipilimumab (Yervoy, anti-CTLA-4), and more recently, the programmed cell death (PD)-1 antibody (pembrolizumab, Keytruda), for the treatment of multiple types of cancer has greatly advanced research and clinical studies in the field of cancer immunotherapy. Furthermore, recent clinical trials, using NY-ESO-1-specific T cell receptor (TCR) or CD19-chimeric antigen receptor (CAR), have shown promising clinical results for patients with metastatic cancer...
January 2017: Cell Research
https://www.readbyqxmd.com/read/28025936/current-status-of-leukemia-cytotherapy-exploitation-with-immune-cells
#18
Haiyan Bao, Depei Wu
With the development of chemotherapy and hematopoietic stem cell transplantation (HSCT), the prognosis of leukemia patients has been improved greatly in the past few decades. However, relapsed and refractory leukemia is still the major cause of mortality in leukemia patients. Besides, advancing age, poor performance status and severe co-morbidities limit the applicability of cytotoxic chemotherapy in certain groups of leukemia patients. Novel agents including nucleoside analogues, kinase inhibitors targeting oncoproteins and monoclonal antibodies are under investigation for the management of leukemia...
December 26, 2016: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28003642/car-t-cell-therapy-of-solid-tumors
#19
REVIEW
Carmen S M Yong, Valerie Dardalhon, Christel Devaud, Naomi Taylor, Phillip K Darcy, Michael H Kershaw
The potential for immunotherapy as a treatment option for cancer is clear from remarkable responses of some leukemia patients to adoptive cell transfer using autologous T cells genetically modified to express chimeric antigen receptors (CARs). However, the vast majority of cancers, in particular the more common solid cancers, such as those of the breast, colon and lung, fail to respond significantly to infusions of CAR T cells. Solid cancers present some formidable barriers to adoptive cell transfer, including suppression of T cell function and inhibition of T cell localization...
December 22, 2016: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28002337/anti-cd19-chimeric-antigen-receptor-t-cell-therapy-for-adult-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-two-case-reports
#20
Yang-Min Zhu, Zhao Wu, You-Ping Tan, Yuan-Yuan Du, Zhi Liu, Rui-Ming Ou, Shuang Liu, Cheng-Fei Pu, Jing Jiang, Jin-Ping Wang, Lei Xiao, Qing Zhang
RATIONALE: The presence of the Philadelphia chromosome (Ph) in acute lymphoblastic leukemia (ALL) has been associated with a high risk of disease relapse and a poor prognosis. Allogeneic hematopoietic stem cell transplantation (HSCT) is an established treatment for adults with Ph-positive ALL, but relapse remains the primary cause of treatment failure, and is associated with an extremely poor prognosis. The emergence of resistance to tyrosine kinase inhibitors (TKIs) poses a challenge for patients with disease relapses after initial treatment with TKI-containing regimens...
December 2016: Medicine (Baltimore)
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