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https://www.readbyqxmd.com/read/29772353/cardiac-profile-of-chimeric-antigen-receptor-car-t-cell-therapy-in-children-a-single-institution-experience
#1
Danielle Burstein, Shannon Maude, Stephen Grupp, Heather Griffis, Joseph Rossano, Kimberly Lin
BACKGROUND: Immunotherapy with chimeric antigen receptor (CAR)-modified T-cells targeting CD19 for pediatric acute lymphoblastic leukemia (ALL) has demonstrated significant efficacy. The principle toxicity is cytokine release syndrome with resultant hypotension. However, the spectrum of cardiovascular effects associated with CAR T-cell therapy has not been systematically evaluated. METHODS: We reviewed all patients who received CD19-directed CAR T-cells at the Children's Hospital of Philadelphia between April 2012 and September 2016...
May 14, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29771253/axicabtagene-ciloleucel-for-the-treatment-of-relapsed-refractory-b-cell-non-hodgkin-s-lymphomas
#2
P Sharma, G T King, S S Shinde, E Purev, A Jimeno
B-cell non-Hodgkin's lymphomas are the most common hematological malignancies, which despite improvements in chemo-immunotherapy, carry a uniformly poor prognosis in the relapsed/refractory setting. CD19 is an antigen expressed on the surface of most malignancies arising from the B cells, and adoptive transfer of anti-CD19 chimeric antigen receptor (CAR)-expressing T cells has been shown to be effective in treating these B-cell malignancies. Axicabtagene ciloleucel (axi-cel, KTE-C19) is an autologous anti-CD19 CAR T-cell therapy which has shown high overall response rates and a manageable safety profile in patients with relapsed or refractory B-cell malignancies who lack effective and curative treatment options...
March 2018: Drugs of Today
https://www.readbyqxmd.com/read/29769444/glioblastoma-targeted-cd4-car-t-cells-mediate-superior-antitumor-activity
#3
Dongrui Wang, Brenda Aguilar, Renate Starr, Darya Alizadeh, Alfonso Brito, Aniee Sarkissian, Julie R Ostberg, Stephen J Forman, Christine E Brown
Chimeric antigen receptor-modified (CAR-modified) T cells have shown promising therapeutic effects for hematological malignancies, yet limited and inconsistent efficacy against solid tumors. The refinement of CAR therapy requires an understanding of the optimal characteristics of the cellular products, including the appropriate composition of CD4+ and CD8+ subsets. Here, we investigated the differential antitumor effect of CD4+ and CD8+ CAR T cells targeting glioblastoma-associated (GBM-associated) antigen IL-13 receptor α2 (IL13Rα2)...
May 17, 2018: JCI Insight
https://www.readbyqxmd.com/read/29769201/in-vitro-priming-of-adoptively-transferred-t-cells-with-a-ror%C3%AE-agonist-confers-durable-memory-and-stemness-in-vivo
#4
Xiao Hu, Kinga Majchrzak, Xikui Liu, Megan M Wyatt, Chauncey Spooner, Jacques Moisan, Weiping Zou, Laura L Carter, Chrystal M Paulos
Adoptive T cell transfer therapy is an FDA-approved treatment for leukemia that relies on the ex vivo expansion and re-infusion of a patient's immune cells, which can be engineered with a chimeric antigen receptor (CAR) for more efficient tumor recognition. Type 17 T cells, controlled transcriptionally by RORγ, have been reported to mediate potent anti-tumor effects superior to those observed with conventionally expanded T cells. Here we demonstrate that addition of a synthetic, small molecule RORγ agonist during ex vivo expansion potentiates the anti-tumor activity of human Th17 and Tc17 cells redirected with a CAR...
May 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29769184/explaining-resistance-to-car-t-cells
#5
(no author information available yet)
A new study reveals several attributes of T cells from patients with chronic lymphocytic leukemia who respond to CAR T-cell therapy. The patients' T cells show increased expression of memory-related genes and high activity of STAT3, which promotes memory cell differentiation. The researchers also found that patients who underwent complete remission have certain CD8+ T cells.
May 16, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29769134/advances-on-chimeric-antigen-receptor-modified-t-cell-therapy-for-oncotherapy
#6
REVIEW
Yanyu Pang, Xiaoyang Hou, Chunsheng Yang, Yanqun Liu, Guan Jiang
Tumor treatment is still complicated in the field of medicine. Tumor immunotherapy has been the most interesting research field in cancer therapy. Application of chimeric antigen receptor T (CAR-T) cell therapy has recently achieved excellent clinical outcome in patients, especially those with CD19-positive hematologic malignancies. This phenomenon has induced intense interest to develop CAR-T cell therapy for cancer, especially for solid tumors. However, the performance of CAR-T cell treatment in solid tumor is not as satisfactory as that in hematologic disease...
May 16, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29768210/engineered-tumor-targeted-t-cells-mediate-enhanced-anti-tumor-efficacy-both-directly-and-through-activation-of-the-endogenous-immune-system
#7
Mauro P Avanzi, Oladapo Yeku, Xinghuo Li, Dinali P Wijewarnasuriya, Dayenne G van Leeuwen, Kenneth Cheung, Hyebin Park, Terence J Purdon, Anthony F Daniyan, Matthew H Spitzer, Renier J Brentjens
Chimeric antigen receptor (CAR) T cell therapy has proven clinically beneficial against B cell acute lymphoblastic leukemia and non-Hodgkin's lymphoma. However, suboptimal clinical outcomes have been associated with decreased expansion and persistence of adoptively transferred CAR T cells, antigen-negative relapses, and impairment by an immunosuppressive tumor microenvironment. Improvements in CAR T cell design are required to enhance clinical efficacy, as well as broaden the applicability of this technology...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29766234/the-severe-cytokine-release-syndrome-in-phase-i-trials-of-cd19-car-t-cell-therapy-a-systematic-review
#8
REVIEW
Zhen Jin, Rufang Xiang, Kai Qing, Xiaoyang Li, Yunxiang Zhang, Lining Wang, Hongming Zhu, Yuanfei Mao, Zizhen Xu, Junmin Li
CD19 chimeric antigen receptor (CAR) T cell therapy has shown impressive results in treating acute lymphoblastic leukemia (B-ALL), chronic lymphoblastic leukemia (B-CLL), and B-cell non-Hodgkin lymphoma (B-NHL) over the past few years. Meanwhile, the cytokine release syndrome (CRS), which could be moderate or even life-threatening, has emerged as the most significant adverse effect in the clinical course of this novel targeting immunotherapy. In this systematic review, we analyzed the incidence of severe CRS in 19 clinical trials selected from studies published between 2010 and 2017...
May 15, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29764166/chimeric-antigen-receptor-t-cells-a-savior-with-a-high-price
#9
Gilberto de Lima Lopes, George R Nahas
Chimeric antigen receptor (CAR) T cells represent a medical and scientific breakthrough that may represent a paradigm for the future of personalized medicine in the age of cancer immunotherapy. As with many new cancer agents, such novel and incredible results come with a high price. At the time of the writing of this article, there are two CAR T cells available, Kymriah, produced by Novrtis with a price tag of US$475,000 and Yescarta produced by Gilead Pharmaceuticals with a price tag of US$373,000, neither price including the required hospital admission in order to administer the agent in addition to potential treatment of side effects...
April 2018: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29764159/emerging-role-of-immunotherapy-for-childhood-cancers
#10
Rupert Handgretinger, Patrick Schlegel
Recent developments in cell and gene therapy have a great impact on the new therapeutic approaches in pediatric cancers. Monoclonal antibodies for neuroblastoma and bispecific antibodies for leukemia have induced significant clinical responses for otherwise chemorefractory patients. Moreover, cellular therapeutic approaches including chimeric antigen receptor (CAR) T-cells as well as natural killer (NK) cells have the potential to cure patients with so far incurable malignancies and are the basis for future new therapies for pediatric cancer...
April 2018: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29760047/nanoparticles-that-reshape-the-tumor-milieu-create-a-therapeutic-window-for-effective-t-cell-therapy-in-solid-malignancies
#11
Fan Zhang, Sirkka B Stephan, Chibawanye I Ene, Tyrel T Smith, Eric C Holland, Matthias T Stephan
A major obstacle to the success rate of chimeric antigen receptor (CAR-) T cell therapy against solid tumors is the microenvironment antagonistic to T cells that solid tumors create. Conventional checkpoint blockade can silence lymphocyte anti-survival pathways activated by tumors, but because they are systemic, these treatments disrupt immune homeostasis and induce autoimmune side effects. Thus, new technologies are required to remodel the tumor milieu without causing systemic toxicities. Here we demonstrate that targeted nanocarriers that deliver a combination of immune-modulatory agents can remove pro-tumor cell populations and simultaneously stimulate anti-tumor effector cells...
May 14, 2018: Cancer Research
https://www.readbyqxmd.com/read/29758187/antigenic-targets-of-car-t-cell-therapy-a-retrospective-view-on-clinical-trials
#12
REVIEW
Fatemeh Arabi, Monireh Torabi-Rahvar, Ali Shariati, Naser Ahmadbeigi, Mahmood Naderi
Chimeric antigen receptor (CAR) T cell therapy is anticipated to be increasingly implemented in the context of cancer treatment after two current FDA approval of anti-CD19 CAR-T cells (KymriahTM & YescartaTM ). The success of CD19 is mainly attributable to the proper selection of the antigen, CD19, as the target of the disease, highlighting the importance of target selection for other CAR therapies. Therefore, here we performed a global analysis of targets that are the prime focus for various CAR-T cell therapies in human clinical trials...
May 11, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29749441/apoptosis-of-cd19-chimeric-antigen-receptor-t-cells-after-treatment-with-chemotherapeutic-agents
#13
Wenfang Yi, Fuyu Pei, Wen Ding, Mo Yang, Guang Lin, Cheng Zhang, Xuedong Wu, Yuelin He, Xiaoqin Feng, Huanying Liu, Zhiyong Peng, Chunfu Li
The use of chemotherapeutic agents prior to treatment with infusion of cluster of differentiation (CD)19-chimeric antigen receptor (CAR)‑T cells is important for the efficacy of clinical therapies against hematological malignancies. However, the effect of chemotherapeutic agents on CD19‑CAR‑T cells and the associated underlying mechanisms remain unknown. The first aim of the present study was to determine the effect of chemotherapeutic agents on CAR‑T cells using the in vitro Cell Counting kit 8 assay...
May 2, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29748183/aberrant-lck-signal-via-cd28-co-stimulation-augments-antigen-specific-functionality-and-tumor-control-by-redirected-t-cells-with-pd-1-blockade-in-humanized-mice
#14
Pratiksha Gulati, Julia Rühl, Abhilash Kannan, Magdalena Pircher, Petra Schuberth, Katarzyna Jozefa Nytko, Martin N Pruschy, Simon Sulser, Mark D Haefner, Shawn M Jensen, Alex Soltermann, Wolfgang Jungraithmayr, Maya Eisenring, Thomas Winder, Panagiotis Samaras, Annett Tabor, Rene Rs Stenger, Roger Stupp, Walter Weder, Christoph Renner, Christian Münz, Ulf Petrausch
PURPOSE: Combination therapy of adoptively transferred redirected T cells and checkpoint inhibitors aims for higher response rates in tumors poorly responsive to immunotherapy like malignant pleural mesothelioma (MPM). Only most recently the issue of an optimally active chimeric antigen receptor (CAR) and the combination with checkpoint inhibitors is starting to be addressed. EXPERIMENTAL DESIGN: Fibroblast Activation Protein (FAP)-specific CARs with different co-stimulatory domains including CD28, Δ-CD28 (lacking lck binding moiety) or 4-1BB were established...
May 10, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29747685/car-t-cell-therapy-for-breast-cancer-harnessing-the-tumor-milieu-to-drive-t-cell-activation
#15
Pradip Bajgain, Supannikar Tawinwung, Lindsey D'Elia, Sujita Sukumaran, Norihiro Watanabe, Valentina Hoyos, Premal Lulla, Malcolm K Brenner, Ann M Leen, Juan F Vera
BACKGROUND: The adoptive transfer of T cells redirected to tumor via chimeric antigen receptors (CARs) has produced clinical benefits for the treatment of hematologic diseases. To extend this approach to breast cancer, we generated CAR T cells directed against mucin1 (MUC1), an aberrantly glycosylated neoantigen that is overexpressed by malignant cells and whose expression has been correlated with poor prognosis. Furthermore, to protect our tumor-targeted cells from the elevated levels of immune-inhibitory cytokines present in the tumor milieu, we co-expressed an inverted cytokine receptor linking the IL4 receptor exodomain with the IL7 receptor endodomain (4/7ICR) in order to transform the suppressive IL4 signal into one that would enhance the anti-tumor effects of our CAR T cells at the tumor site...
May 10, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29741512/advances-in-car-t-cell-therapy-for-chronic-lymphocytic-leukemia
#16
David L Porter
No abstract text is available yet for this article.
February 2018: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29735365/human-cd19-targeted-mouse-t-cells-induce-b-cell-aplasia-and-toxicity-in-human-cd19-transgenic-mice
#17
Christopher A Pennell, Jessie L Barnum, Cameron S McDonald-Hyman, Angela Panoskaltsis-Mortari, Megan J Riddle, Zhengming Xiong, Michael Loschi, Govindarajan Thangavelu, Heather M Campbell, Meghan D Storlie, Yosef Refaeli, Scott N Furlan, Michael C Jensen, Leslie S Kean, Jeffrey S Miller, Jakub Tolar, Mark J Osborn, Bruce R Blazar
The clinical success of chimeric antigen receptor (CAR) T cell therapy for CD19+ B cell malignancies can be limited by acute toxicities and immunoglobulin replacement needs due to B cell aplasia from persistent CAR T cells. Life-threatening complications include cytokine release syndrome and neurologic adverse events, the exact etiologies of which are unclear. To elucidate the underlying toxicity mechanisms and test potentially safer CAR T cells, we developed a mouse model in which human CD19 (hCD19)-specific mouse CAR T cells were adoptively transferred into mice whose normal B cells express a hCD19 transgene at hemizygous levels...
April 7, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29734306/allogene-and-celularity-move-car-t-therapy-off-the-shelf
#18
Cormac Sheridan
No abstract text is available yet for this article.
May 9, 2018: Nature Biotechnology
https://www.readbyqxmd.com/read/29730801/challenges-and-prospects-of-chimeric-antigen-receptor-t-cell-therapy-in-solid-tumors
#19
REVIEW
Vishal Jindal, Ena Arora, Sorab Gupta
Chimeric antigen receptor (CAR) T cell therapy is a novel and innovative immunotherapy. CAR-T cells are genetically engineered T cells, carrying MHC independent specific antigen receptor and co-stimulatory molecule which can activate an immune response to a cancer specific antigen. This therapy showed great results in hematological malignancies but were unable to prove their worth in solid tumors. Likely reasons for their failure are lack of antigens, poor trafficking, and hostile tumor microenvironment. Excessive amount of research is going on to improve the efficacy of CAR T cell therapy in solid tumors...
May 5, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29730080/a-decade-of-marketing-approval-of-gene-and-cell-based-therapies-in-the-united-states-european-union-and-japan-an-evaluation-of-regulatory-decision-making
#20
D G M Coppens, S de Wilde, H J Guchelaar, M L De Bruin, H G M Leufkens, P Meij, J Hoekman
There is a widely held expectation of clinical advance with the development of gene and cell-based therapies (GCTs). Yet, establishing benefits and risks is highly uncertain. We examine differences in decision-making for GCT approval between jurisdictions by comparing regulatory assessment procedures in the United States (US), European Union (EU) and Japan. A cohort of 18 assessment procedures was analyzed by comparing product characteristics, evidentiary and non-evidentiary factors considered for approval and post-marketing risk management...
May 2, 2018: Cytotherapy
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