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https://www.readbyqxmd.com/read/29682521/immune-escape-mechanisms-and-future-prospects-for-immunotherapy-in-neuroblastoma
#1
REVIEW
Thitinee Vanichapol, Somchai Chutipongtanate, Usanarat Anurathapan, Suradej Hongeng
Neuroblastoma (NB) is the most common extracranial solid tumor in childhood with 5-year survival rate of 40% in high-risk patients despite intensive therapies. Recently, adoptive cell therapy, particularly chimeric antigen receptor (CAR) T cell therapy, represents a revolutionary treatment for hematological malignancies. However, there are challenges for this therapeutic strategy with solid tumors, as a result of the immunosuppressive nature of the tumor microenvironment (TME). Cancer cells have evolved multiple mechanisms to escape immune recognition or to modulate immune cell function...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29678834/from-pluripotent-stem-to-car-t-cells
#2
(no author information available yet)
Within the field of allogeneic chimeric antigen receptor T-cell therapy, La Jolla, CA-based Fate Therapeutics is exploring in vitro differentiation of induced pluripotent stem cells, rather than T cells harvested from donors, as their source material. Preclinical data on the company's off-the-shelf candidate, FT819, look promising so far.
April 20, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29678657/development-and-evaluation-of-an-optimal-human-single-chain-variable-fragment-derived-bcma-targeted-car-t-cell-vector
#3
Eric L Smith, Mette Staehr, Reed Masakayan, Ishan J Tatake, Terence J Purdon, Xiuyan Wang, Pei Wang, Hong Liu, Yiyang Xu, Sarah C Garrett-Thomson, Steven C Almo, Isabelle Riviere, Cheng Liu, Renier J Brentjens
B cell maturation antigen (BCMA) has recently been identified as an important multiple myeloma (MM)-specific target for chimeric antigen receptor (CAR) T cell therapy. In CAR T cell therapy targeting CD19 for lymphoma, host immune anti-murine CAR responses limited the efficacy of repeat dosing and possibly long-term persistence. This clinically relevant concern can be addressed by generating a CAR incorporating a human single-chain variable fragment (scFv). We screened a human B cell-derived scFv phage display library and identified a panel of BCMA-specific clones from which human CARs were engineered...
March 28, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29678194/the-perfect-personalized-cancer-therapy-cancer-vaccines-against-neoantigens
#4
REVIEW
Luigi Aurisicchio, Matteo Pallocca, Gennaro Ciliberto, Fabio Palombo
In the advent of Immune Checkpoint inhibitors (ICI) and of CAR-T adoptive T-cells, the new frontier in Oncology is Cancer Immunotherapy because of its ability to provide long term clinical benefit in metastatic disease in several solid and liquid tumor types. It is now clear that ICI acts by unmasking preexisting immune responses as well as by inducing de novo responses against tumor neoantigens. Thanks to theprogress made in genomics technologies and the evolution of bioinformatics, neoantigens represent ideal targets, due to their specific expression in cancer tissue and the potential lack of side effects...
April 20, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29677416/car-t-cell-immunotherapy-bringing-hope-where-none-existed
#5
Joseph E Kerschner
No abstract text is available yet for this article.
March 2018: WMJ: Official Publication of the State Medical Society of Wisconsin
https://www.readbyqxmd.com/read/29676233/chimeric-antigen-receptor-t-cell-based-immunotherapy-for-cancer
#6
Feng Li, Tengfei Zhang, Ling Cao, Yi Zhang
Cancer immunotherapy, a new weapon against cancers by harnessing the patient's own immune system, potentiates an extended remission and possibly a cure for cancer. T cells genetically engineered with chimeric antigen receptor (CAR) vectors can specifically target the surface antigen of cancer cells and kill them in an MHC-independent manner. CD19 is extensively expressed on cancerous cells in B cell malignancies. To target this antigen, CAR T cells have gained great success in treating patients with B cell leukemia and lymphoma...
April 19, 2018: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29669947/anti-cd19-car-t-cells-with-high-dose-melphalan-and-autologous-stem-cell-transplantation-for-refractory-multiple-myeloma
#7
Alfred L Garfall, Edward A Stadtmauer, Wei-Ting Hwang, Simon F Lacey, Jan Joseph Melenhorst, Maria Krevvata, Martin P Carroll, William H Matsui, Qiuju Wang, Madhav V Dhodapkar, Kavita Dhodapkar, Rituparna Das, Dan T Vogl, Brendan M Weiss, Adam D Cohen, Patricia A Mangan, Emily C Ayers, Selene Nunez-Cruz, Irina Kulikovskaya, Megan M Davis, Anne Lamontagne, Karen Dengel, Naseem Ds Kerr, Regina M Young, Donald L Siegel, Bruce L Levine, Michael C Milone, Marcela V Maus, Carl H June
BACKGROUND: Multiple myeloma is usually fatal due to serial relapses that become progressively refractory to therapy. CD19 is typically absent on the dominant multiple myeloma cell population but may be present on minor subsets with unique myeloma-propagating properties. To target myeloma-propagating cells, we clinically evaluated autologous T cells transduced with a chimeric antigen receptor (CAR) against CD19 (CTL019). METHODS: Subjects received CTL019 following salvage high-dose melphalan and autologous stem cell transplantation (ASCT)...
April 19, 2018: JCI Insight
https://www.readbyqxmd.com/read/29668614/arthritis-of-large-joints-shown-as-a-rare-clinical-feature-of-cytokine-release-syndrome-after-chimeric-antigen-receptor-t-cell-therapy-a-case-report
#8
Li-Xin Wang, Xiaoping Chen, Mingming Jia, Shengdian Wang, Jianliang Shen
RATIONALE: Chimeric antigen receptor (CAR)-T cell therapy is a novel type of therapy that is being used in an increasing number of patients with acute lymphoblastic leukemia (ALL). Cytokine release syndrome (CRS) is the most common complication following CAR-T treatment, but the current understanding of the clinical manifestations and pathogenesis of CRS is still limited. PATIENT CONCERNS: A 34-year-old male patient was diagnosed with ALL in June 2015. Complete remission (CR) was achieved after induction chemotherapy...
April 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29667553/car-t-cell-therapy-a-new-era-in-cancer-immunotherapy
#9
Miliotou N Androulla, Papadopoulou C Lefkothea
BACKGROUND: Cancer is one of the leading causes of death worldwide. Over the years, a number of conventional cytotoxic approaches for neoplastic diseases has been developed. However, due to their limited effectiveness in accordance with the heterogeneity of cancer cells, there is a constant search for therapeutic approaches with improved outcome, such as immunotherapy that utilizes and enhances the normal capacity of the patient's immune system. METHODS: Chimeric Antigen Receptor (CAR) T-cell therapy involves genetic modification of patient's autologous T-cells to express a CAR specific for a tumor antigen, following by ex vivo cell expansion and re-infusion back to the patient...
April 17, 2018: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/29666934/quo-vadis-do-immunotherapies-have-a-role-in-glioblastoma
#10
REVIEW
Sylvia C Kurz, Patrick Y Wen
PURPOSE OF REVIEW: More effective therapies for glioblastoma are urgently needed. Immunotherapeutic strategies appear particularly promising and are therefore intensively studied. This article reviews the current understanding of the immunosuppressive glioblastoma microenvironment, discusses the rationale behind various immunotherapies, and outlines the findings of several recently published clinical studies. RECENT FINDINGS: The results of CheckMate-143 indicated that nivolumab is not superior to bevacizumab in patients with recurrent glioblastoma...
April 18, 2018: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/29665944/-current-status-and-challenges-of-car-t-immunotherapy-in-hematologic-malignancies-review
#11
Xin Cheng, Ya-Jie Wang, Shuai Feng, Ya-Yun Wu, Tong-Hua Yang, Xun Lai
The chimeric antigen receptor (CAR) T cell therapy has gradually became a new trend in the treatment of refractory and relapsed hematologic malignancies by developing for 30 years. With the exciting development of genetic engineering, CAR-T technology has subjected to 4 generations of innovation. Structure of CAR-T started from a single signal molecule to 2 or more than 2 co-stimulatory molecules, and then coding the CAR gene or promoter. CAR-T can specifically recognize tumor antigens, and does not be restricted by major histocompatibility complex (MHC), thus making a breakthrough in clinical treatment...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29662667/genetically-enhanced-t-lymphocytes-and-the-intensive-care-unit
#12
REVIEW
Tiberiu Tat, Huming Li, Catalin-Sorin Constantinescu, Anca Onaciu, Sergiu Chira, Ciprian Osan, Sergiu Pasca, Bobe Petrushev, Vlad Moisoiu, Wilhelm-Thomas Micu, Cristian Berce, Sebastian Tranca, Delia Dima, Ioana Berindan-Neagoe, Jianliang Shen, Ciprian Tomuleasa, Liren Qian
Chimeric antigen receptor-modified T cells (CAR-T cells) and donor lymphocyte infusion (DLI) are important protocols in lymphocyte engineering. CAR-T cells have emerged as a new modality for cancer immunotherapy due to their potential efficacy against hematological malignancies. These genetically modified receptors contain an antigen-binding moiety, a hinge region, a transmembrane domain, and an intracellular costimulatory domain resulting in lymphocyte T cell activation subsequent to antigen binding. In present-day medicine, four generations of CAR-T cells are described depending on the intracellular signaling domain number of T cell receptors...
March 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29662316/metformin-inhibits-proliferation-and-cytotoxicity-and-induces-apoptosis-via-ampk-pathway-in-cd19-chimeric-antigen-receptor-modified-t-cells
#13
Qian Mu, Miao Jiang, Yuzhu Zhang, Fei Wu, Hui Li, Wen Zhang, Fang Wang, Jiang Liu, Liang Li, Dongshan Wang, Wenjuan Wang, Shiwu Li, Haibo Song, Dongqi Tang
Background: CD19-chimericantigen receptor (CAR) modified T cells (CD19-CAR T cells) have been well documented to possess potent anti-tumor properties against CD19-expressingleukemia cells. As a traditional medicine, metformin has been widely used to treat type II diabetes mellitus and more recently has become a candidate for the treatment of cancer. However, no report has revealed the direct effect of metformin on CD19-CAR T cell biological function and its underling mechanisms. Purpose: The purpose of this research was to explore the effect of metformin on CD19-CAR T cell biological function and the mechanisms involved...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29662203/potent-antitumor-efficacy-of-anti-gd2-car-t-cells-in-h3-k27m-diffuse-midline-gliomas
#14
Christopher W Mount, Robbie G Majzner, Shree Sundaresh, Evan P Arnold, Meena Kadapakkam, Samuel Haile, Louai Labanieh, Esther Hulleman, Pamelyn J Woo, Skyler P Rietberg, Hannes Vogel, Michelle Monje, Crystal L Mackall
Diffuse intrinsic pontine glioma (DIPG) and other diffuse midline gliomas (DMGs) with mutated histone H3 K27M (H3-K27M)1-5 are aggressive and universally fatal pediatric brain cancers 6 . Chimeric antigen receptor (CAR)-expressing T cells have mediated impressive clinical activity in B cell malignancies7-10 , and recent results suggest benefit in central nervous system malignancies11-13 . Here, we report that patient-derived H3-K27M-mutant glioma cell cultures exhibit uniform, high expression of the disialoganglioside GD2...
April 16, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29661681/a-rapamycin-activated-caspase-9-based-suicide-gene
#15
Maria Stavrou, Brian Philip, Charlotte Traynor-White, Christopher G Davis, Shimobi Onuoha, Shaun Cordoba, Simon Thomas, Martin Pule
Engineered T cell therapies show considerable promise in the treatment of refractory malignancies. Given the ability of engineered T cells to engraft and persist for prolonged periods along with unpredicted toxicities, incorporation of a suicide gene to allow selective depletion after administration is desirable. Rapamycin is a safe and widely available immunosuppressive pharmaceutical that acts by heterodimerization of FKBP12 with the FRB fragment of mTOR. The apical caspase caspase 9 is activated by homodimerization through its CARD domain...
March 9, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29655962/novel-targets-and-technologies-for-car-t-cells-in-multiple-myeloma-and-acute-myeloid-leukemia
#16
EDITORIAL
Sabrina Prommersberger, Hardikkumar Jetani, Sophia Danhof, Razieh Monjezi, Thomas Nerreter, Julia Beckmann, Herrmann Einsele, Michael Hudecek
No abstract text is available yet for this article.
April 11, 2018: Current Research in Translational Medicine
https://www.readbyqxmd.com/read/29655961/chimeric-antigen-receptor-t-cell-therapy-for-non-hodgkin-lymphoma
#17
REVIEW
Armin Ghobadi
Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy. More than 20,000 people in United States, more than 37,000 people in Europe and more than 199,000 people worldwide die of NHL every year. Recent advances in immunotherapeutic approaches for cancer have resulted in development of new classes of very effective immunotherapeutic approaches including chimeric antigen receptor T (CAR-T) cell therapy that are designed to bypass cancer immune evasion. Here, we review recent advances in CAR-T cell therapy for NHL...
April 11, 2018: Current Research in Translational Medicine
https://www.readbyqxmd.com/read/29651744/prospects-of-chimeric-antigen-receptor-t-cell-therapy-in-ovarian-cancer
#18
REVIEW
Vishal Jindal, Ena Arora, Sorab Gupta, Amos Lal, Muhammad Masab, Rashmika Potdar
Despite advances in various chemotherapy regimens, current therapeutic options are limited for ovarian cancer patients. Immunotherapy provides a promising and novel treatment option for ovarian cancer. Recently, chimeric antigen receptor (CAR) T cell therapy has shown promising results in hematological tumors and current research is going on in various solid tumors like ovarian cancer. CAR T cells are genetically engineered T cells with major histocompatibility complex-independent, tumor-specific, immune-mediated cytolytic actions against cancer cells...
April 12, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29648659/comment-on-trivalent-car-t-cells-overcome-interpatient-antigenic-variability-in-glioblastoma
#19
Hillary Caruso, Amy B Heimberger
No abstract text is available yet for this article.
April 10, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29628798/versatile-car-t-cells-for-cancer-immunotherapy
#20
REVIEW
Fuliang Chu, Jingjing Cao, Sattva S Neelalpu
Chimeric antigen receptor (CAR) T-cell therapy has been clinically proven to efficiently combat haematological malignancies. However, continuous efforts are required to increase the specificity of CAR T-cells against tumour versus normal tissues, and are essential to improve their antitumour activity in solid tumours. This review summarises the structure of major CAR designs, and strategies to overcome immunosuppressive tumour microenvironment, and reduce toxicities. Along with reviewing currently available techniques that allow the elimination of CAR T-cells after they fulfil their desired functions, using suicide genes, drug elimination strategies are also introduced...
March 2018: Contemporary Oncology Współczesna Onkologia
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