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Chimeric antigen

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https://www.readbyqxmd.com/read/28093489/correction-the-future-is-now-chimeric-antigen-receptors-as-new-targeted-therapies-for-childhood-cancer
#1
(no author information available yet)
No abstract text is available yet for this article.
January 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28090317/all-trans-retinoic-acid-enhances-cytotoxic-effect-of-t-cells-with-an-anti-cd38-chimeric-antigen-receptor-in-acute-myeloid-leukemia
#2
Tetsumi Yoshida, Keichiro Mihara, Yoshifumi Takei, Kazuyoshi Yanagihara, Takanori Kubo, Joyeeta Bhattacharyya, Chihaya Imai, Tatsuji Mino, Yoshihiro Takihara, Tatsuo Ichinohe
We reported that T cells with anti-CD38-chimeric antigen receptors (CAR) eliminated B-cell lymphoma cells expressing CD38. To employ anti-CD38-CAR against acute myeloid leukemia (AML) blasts not expressing CD38, it is necessary to induce or increase the intensity of CD38 expression. A lactate dehydrogenase (LDH)-releasing assay and flow cytometry showed that anti-CD38-CAR T cells were cytotoxic against AML lines (THP-1 and CMK) expressing high CD38 levels (>99%), in time- and number of effector-dependent manners...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28089834/recent-clinical-trials-utilizing-chimeric-antigen-receptor-t-cells-therapies-against-solid-tumors
#3
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
#4
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
#5
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/28074066/preclinical-targeting-of-aggressive-t-cell-malignancies-using-anti-cd5-chimeric-antigen-receptor
#6
K H Chen, M Wada, K G Pinz, H Liu, K-W Lin, A Jares, A E Firor, X Shuai, H Salman, M Golightly, F Lan, L Senzel, L-H Leung, X Jiang, Y Ma
The outlook for T-cell malignancies remain poor due to the lack of effective therapeutic options. Chimeric antigen receptor (CAR) immunotherapy has recently shown promise in clinical trials for B-cell malignancies, however, designing CARs for T-cell based disease remain a challenge due to the shared surface antigen pool between normal and malignant T-cells. Normal T-cells express CD5 but NK (natural killer) cells do not, positioning NK cells as attractive cytotoxicity cells for CD5CAR design. Additionally, CD5 is highly expressed in T cell acute lymphoblastic leukemia (T-ALL) and peripheral T cell lymphomas (PTCLs)...
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28071584/major-highlights-of-the-car-tcr-summit-boston-2016
#7
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/28070500/chimeric-influenza-haemagglutinins-generation-and-use-in-pseudotype-neutralization-assays
#8
Francesca Ferrara, Nigel Temperton
Recently chimeric influenza haemagglutinins (cHAs) have been generated as potential 'universal' vaccination antigens and as tools to identify HA stalk-directed antibodies via their use as antigens in ELISA, and virus or pseudotype-based neutralization assays. The original methods [1], [2] used for their generation require the amplification of regions of interest (head and stalk) using primers containing SapI sites and subsequent cloning into pDZ plasmid. This requires precise primer design, checking for the absence of SapI sites in the sequence of interest, and multi-segment ligation...
2017: MethodsX
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/28067290/chimeric-virus-like-particles-containing-influenza-ha-antigen-and-gpi-ccl28-induce-long-lasting-mucosal-immunity-against-h3n2-viruses
#11
Teena Mohan, Zachary Berman, Yuan Luo, Chao Wang, Shelly Wang, Richard W Compans, Bao-Zhong Wang
Influenza virus is a significant cause of morbidity and mortality, with worldwide seasonal epidemics. The duration and quality of humoral immunity and generation of immunological memory to vaccines is critical for protective immunity. In the current study, we examined the long-lasting protective efficacy of chimeric VLPs (cVLPs) containing influenza HA and GPI-anchored CCL28 as antigen and mucosal adjuvant, respectively, when immunized intranasally in mice. We report that the cVLPs induced significantly higher and sustainable levels of virus-specific antibody responses, especially IgA levels and hemagglutination inhibition (HAI) titers, more than 8-month post-vaccination compared to influenza VLPs without CCL28 or influenza VLPs physically mixed with sCCL28 (soluble) in mice...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28067225/hepatitis-c-virus-has-a-genetically-determined-lymphotropism-through-co-receptor-b7-2
#12
Chia-Lin Chen, Jeffrey Y Huang, Chun-Hsiang Wang, Stanley M Tahara, Lin Zhou, Yasuteru Kondo, Joel Schechter, Lishan Su, Michael M C Lai, Takaji Wakita, François-Loïc Cosset, Jae U Jung, Keigo Machida
B-cell infection by hepatitis C virus (HCV) has been a controversial topic. To examine whether HCV has a genetically determined lymphotropism through a co-receptor specific for the infection by lymphotropic HCV, we established an infectious clone and chimeric virus of hepatotropic and lymphotropic HCV strains derived from an HCV-positive B-cell lymphoma. The viral envelope and 5'-UTR sequences of the lymphotropic HCV strain were responsible for the lymphotropism. Silencing of the virus sensor, RIGI, or overexpression of microRNA-122 promoted persistent viral replication in B cells...
January 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28067179/cd20-based-immunotherapy-of-b-cell-derived-hematologic-malignancies
#13
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
#14
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
#15
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
#16
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/28055955/chimeric-antigen-receptor-modified-t-cells-inhibit-the-growth-and-metastases-of-established-tissue-factor-positive-tumors-in-nog-mice
#17
Qing Zhang, Haiyu Wang, Huizhong Li, Jinjing Xu, Kang Tian, Jie Yang, Zheng Lu, Junnian Zheng
Chimeric antigen receptor (CAR)-modified T cell (CAR T) is a promising therapeutic option for patients with cancer. Such an approach requires the identification of tumor-specific antigen targets that are expressed in solid tumors. We developed a new third-generation CAR directed against tissue factor (TF), a surface molecule overexpressed in some types of lung cancer, melanoma and other cancers. First, we demonstrated by immunohistochemistry that TF was overexpressed in squamous cell carcinoma and adenocarcinoma of non-small cell lung cancer (NSCLC) and melanoma using a human tissue microarray...
December 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/28053197/chimeric-antigen-receptor-t-cells-therapy-for-tumor-immunotherapy
#18
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
#19
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/28049548/chimeric-antigen-receptor-t-cell-neuropsychiatric-toxicity-in-acute-lymphoblastic-leukemia
#20
Vasthie Prudent, William S Breitbart
Chimeric antigen receptor T cells are used in the treatment of B-cell leukemias. Common chimeric antigen receptor T-cell toxicities can range from mild flu-like symptoms, such as fever and myalgia, to a more striking neuropsychiatric toxicity that can present as discrete neurological symptoms and delirium. We report here two cases of chimeric antigen receptor T-cell neuropsychiatric toxicity, one who presented as a mild delirium and aphasia that resolved without intervention, and one who presented with delirium, seizures, and respiratory insufficiency requiring intensive treatment...
January 4, 2017: Palliative & Supportive Care
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