keyword
MENU ▼
Read by QxMD icon Read
search

Car t-cell therapy

keyword
https://www.readbyqxmd.com/read/28436934/biopolymers-codelivering-engineered-t-cells-and-sting-agonists-can-eliminate-heterogeneous-tumors
#1
Tyrel T Smith, Howell F Moffett, Sirkka B Stephan, Cary F Opel, Amy G Dumigan, Xiuyun Jiang, Venu G Pillarisetty, Smitha P S Pillai, K Dane Wittrup, Matthias T Stephan
Therapies using T cells that are programmed to express chimeric antigen receptors (CAR T cells) consistently produce positive results in patients with hematologic malignancies. However, CAR T cell treatments are less effective in solid tumors for several reasons. First, lymphocytes do not efficiently target CAR T cells; second, solid tumors create an immunosuppressive microenvironment that inactivates T cell responses; and third, solid cancers are typified by phenotypic diversity and thus include cells that do not express proteins targeted by the engineered receptors, enabling the formation of escape variants that elude CAR T cell targeting...
April 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28434148/advancing-chimeric-antigen-receptor-t-cell-therapy-with-crispr-cas9
#2
REVIEW
Jiangtao Ren, Yangbing Zhao
The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (CRISPR/Cas9) system, an RNA-guided DNA targeting technology, is triggering a revolution in the field of biology. CRISPR/Cas9 has demonstrated great potential for genetic manipulation. In this review, we discuss the current development of CRISPR/Cas9 technologies for therapeutic applications, especially chimeric antigen receptor (CAR) T cell-based adoptive immunotherapy. Different methods used to facilitate efficient CRISPR delivery and gene editing in T cells are compared...
April 22, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28434147/increasing-the-safety-and-efficacy-of-chimeric-antigen-receptor-t-cell-therapy
#3
REVIEW
Hua Li, Yangbing Zhao
Chimeric antigen receptor (CAR) T cell therapy is a promising cancer treatment that has recently been undergoing rapid development. However, there are still some major challenges, including precise tumor targeting to avoid off-target or "on-target/off-tumor" toxicity, adequate T cell infiltration and migration to solid tumors and T cell proliferation and persistence across the physical and biochemical barriers of solid tumors. In this review, we focus on the primary challenges and strategies to design safe and effective CAR T cells, including using novel cutting-edge technologies for CAR and vector designs to increase both the safety and efficacy, further T cell modification to overcome the tumor-associated immune suppression, and using gene editing technologies to generate universal CAR T cells...
April 22, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28433515/understanding-clinical-development-of-chimeric-antigen-receptor-t-cell-therapies
#4
Sofieke de Wilde, Henk-Jan Guchelaar, Maarten Laurens Zandvliet, Pauline Meij
BACKGROUND AIMS: In the past decade, many clinical trials with gene- and cell-based therapies (GCTs) have been performed. Increased interest in the development of these drug products by various stakeholders has become apparent. Despite this growth in clinical studies, the number of therapies receiving marketing authorization approval (MAA) is lagging behind. To enhance the success rate of GCT development, it is essential to better understand the clinical development of these products...
April 19, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28428885/the-why-what-and-how-of-the-new-fact-standards-for-immune-effector-cells
#5
EDITORIAL
Marcela V Maus, Sarah Nikiforow
Novel cellular therapies outside of traditional hematopoietic stem cell transplantation or hematopoietic progenitor cell (HPC) therapy are currently under evaluation in clinical trials across the United States and around the world. Several cellular products, e.g., CD19-directed Chimeric Antigen Receptor (CAR) T cells, are poised for FDA approval and thus increased use at a wider range of academic centers within the next year, with the likelihood of dissemination to standard oncology practice once safety is confirmed...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28428443/mechanisms-of-pinometostat-epz-5676-treatment-emergent-resistance-in-mll-rearranged-leukemia
#6
Carly T Campbell, Jessica N Haladyna, David A Drubin, Ty M Thomson, Michael J Maria, Taylor Yamauchi, Nigel J Waters, Edward J Olhava, Roy M Pollock, Jesse J Smith, Robert A Copeland, Stephen J Blakemore, Kathrin M Bernt, Scott R Daigle
DOT1L is a protein methyltransferase involved in the development and maintenance of MLL-rearranged (MLL-r) leukemia through its ectopic methylation of histones associated with well characterized leukemic genes.  Pinometostat (EPZ-5676), a selective inhibitor of DOT1L, is in clinical development in relapsed/refractory acute leukemia patients harboring rearrangements of the MLL gene. The observation of responses and subsequent relapses in the adult trial treating MLL-r patients motivated preclinical investigations into potential mechanisms of pinometostat treatment emergent resistance (TER) in cell lines confirmed to have MLL-r...
April 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28421069/engineering-chimeric-antigen-receptor-t-cells-for-racing-in-solid-tumors-don-t-forget-the-fuel
#7
REVIEW
Melita Irving, Romain Vuillefroy de Silly, Kirsten Scholten, Nahzli Dilek, George Coukos
T-cells play a critical role in tumor immunity. Indeed, the presence of tumor-infiltrating lymphocytes is a predictor of favorable patient prognosis for many indications and is a requirement for responsiveness to immune checkpoint blockade therapy targeting programmed cell death 1. For tumors lacking immune infiltrate, or for which antigen processing and/or presentation has been downregulated, a promising immunotherapeutic approach is chimeric antigen receptor (CAR) T-cell therapy. CARs are hybrid receptors that link the tumor antigen specificity and affinity of an antibody-derived single-chain variable fragment with signaling endodomains associated with T-cell activation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28416815/in-situ-programming-of-leukaemia-specific-t-cells-using-synthetic-dna-nanocarriers
#8
Tyrel T Smith, Sirkka B Stephan, Howell F Moffett, Laura E McKnight, Weihang Ji, Diana Reiman, Emmy Bonagofski, Martin E Wohlfahrt, Smitha P S Pillai, Matthias T Stephan
An emerging approach for treating cancer involves programming patient-derived T cells with genes encoding disease-specific chimeric antigen receptors (CARs), so that they can combat tumour cells once they are reinfused. Although trials of this therapy have produced impressive results, the in vitro methods they require to generate large numbers of tumour-specific T cells are too elaborate for widespread application to treat cancer patients. Here, we describe a method to quickly program circulating T cells with tumour-recognizing capabilities, thus avoiding these complications...
April 17, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28416139/cars-synthetic-immunoreceptors-for-cancer-therapy-and-beyond
#9
REVIEW
ZeNan L Chang, Yvonne Y Chen
Chimeric antigen receptors (CARs) are versatile synthetic receptors that provide T cells with engineered specificity. Clinical success in treating B-cell malignancies has demonstrated the therapeutic potential of CAR-T cells against cancer, and efforts are underway to expand the use of engineered T cells to the treatment of diverse medical conditions, including infections and autoimmune diseases. Here, we review current understanding of the molecular properties of CARs, how this knowledge informs the rational design and characterization of novel receptors, the successes and shortcomings of CAR-T cells in the clinic, and emerging solutions for the continued improvement of CAR-T cell therapy...
April 13, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28413717/advances-of-cd19-directed-chimeric-antigen-receptor-modified-t-cells-in-refractory-relapsed-acute-lymphoblastic-leukemia
#10
REVIEW
Guoqing Wei, Lijuan Ding, Jiasheng Wang, Yongxian Hu, He Huang
Refractory/relapsed B-cell acute lymphoblastic leukemia remains to be a significant cause of cancer-associated morbidity and mortality for children and adults. Developing novel and effective molecular-targeted approaches is thus a major priority. Chimeric antigen receptor-modified T cell (CAR-T) therapy, as one of the most promising targeted immunotherapies, has drawn extensive attention and resulted in multiple applications. According to published studies, CD19-directed CAR-T cells (CD19 CAR-T) can reach a complete remission rate of 94% in both children and adults with refractory/relapsed ALL, much higher than that of chemotherapy...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28411126/low-interleukin-2-concentration-favors-generation-of-early-memory-t-cells-over-effector-phenotypes-during-chimeric-antigen-receptor-t-cell-expansion
#11
Tanja Kaartinen, Annu Luostarinen, Pilvi Maliniemi, Joni Keto, Mikko Arvas, Heini Belt, Jonna Koponen, Angelica Loskog, Satu Mustjoki, Kimmo Porkka, Seppo Ylä-Herttuala, Matti Korhonen
BACKGROUND: Adoptive T-cell therapy offers new options for cancer treatment. Clinical results suggest that T-cell persistence, depending on T-cell memory, improves efficacy. The use of interleukin (IL)-2 for in vitro T-cell expansion is not straightforward because it drives effector T-cell differentiation but does not promote the formation of T-cell memory. We have developed a cost-effective expansion protocol for chimeric antigen receptor (CAR) T cells with an early memory phenotype...
April 11, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28408724/from-protection-to-entitlement-selecting-research-subjects-for-early-phase-clinical-trials-involving-breakthrough-therapies
#12
Nancy S Jecker, Aaron G Wightman, Abby R Rosenberg, Douglas S Diekema
Our goals are to (1) set forth and defend a multiprinciple system for selecting individuals who meet trial eligibility criteria to participate in early phase clinical trials testing chimeric antigen receptor (CAR T-cell) for acute lymphoblastic leukaemia when demand for participation exceeds spaces available in a trial; (2) show the relevance of these selection criteria to other breakthrough experimental therapies; (3) argue that distinct distributive justice criteria apply to breakthrough experimental therapies, standard research and healthcare and (4) argue that as evidence of benefit increases, the emphasis of justice in research shifts from protecting subjects from harm to ensuring fair access to benefits...
April 13, 2017: Journal of Medical Ethics
https://www.readbyqxmd.com/read/28407743/new-drugs-new-toxicities-severe-side-effects-of-modern-targeted-and-immunotherapy-of-cancer-and-their-management
#13
REVIEW
Frank Kroschinsky, Friedrich Stölzel, Simone von Bonin, Gernot Beutel, Matthias Kochanek, Michael Kiehl, Peter Schellongowski
Pharmacological and cellular treatment of cancer is changing dramatically with benefits for patient outcome and comfort, but also with new toxicity profiles. The majority of adverse events can be classified as mild or moderate, but severe and life-threatening complications requiring ICU admission also occur. This review will focus on pathophysiology, symptoms, and management of these events based on the available literature.While standard antineoplastic therapy is associated with immunosuppression and infections, some of the recent approaches induce overwhelming inflammation and autoimmunity...
April 14, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/28405508/antigen-receptor-redirected-t-cells-derived-from-hematopoietic-precursor-cells-lack-expression-of-the-endogenous-tcr-cd3-receptor-and-exhibit-specific-antitumor-capacities
#14
Yasmine Van Caeneghem, Stijn De Munter, Paola Tieppo, Glenn Goetgeluk, Karin Weening, Greet Verstichel, Sarah Bonte, Tom Taghon, Georges Leclercq, Tessa Kerre, Reno Debets, David Vermijlen, Hinrich Abken, Bart Vandekerckhove
Recent clinical studies indicate that adoptive T-cell therapy and especially chimeric antigen receptor (CAR) T-cell therapy is a very potent and potentially curative treatment for B-lineage hematologic malignancies. Currently, autologous peripheral blood T cells are used for adoptive T-cell therapy. Adoptive T cells derived from healthy allogeneic donors may have several advantages; however, the expected occurrence of graft versus host disease (GvHD) as a consequence of the diverse allogeneic T-cell receptor (TCR) repertoire expressed by these cells compromises this approach...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28402189/going-non-viral-the-sleeping-beauty-transposon-system-breaks-on-through-to-the-clinical-side
#15
Michael Hudecek, Zsuzsanna Izsvák, Sandra Johnen, Matthias Renner, Gabriele Thumann, Zoltán Ivics
Molecular medicine has entered a high-tech age that provides curative treatments of complex genetic diseases through genetically engineered cellular medicinal products. Their clinical implementation requires the ability to stably integrate genetic information through gene transfer vectors in a safe, effective and economically viable manner. The latest generation of Sleeping Beauty (SB) transposon vectors fulfills these requirements, and may overcome limitations associated with viral gene transfer vectors and transient non-viral gene delivery approaches that are prevalent in ongoing pre-clinical and translational research...
April 12, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28400417/car-t-cell-therapy-defining-response-characteristics
#16
(no author information available yet)
Findings from a phase I study suggest that the durability of patients' response to CAR T-cell therapy, and their long-term survival, are influenced by whether they have minimal residual or morphologic disease prior to treatment. The former fared better overall, and also experienced less-severe side effects from this form of immunotherapy.
April 11, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28389661/crispr-cas9-mediated-pd-1-disruption-enhances-anti-tumor-efficacy-of-human-chimeric-antigen-receptor-t-cells
#17
Levi J Rupp, Kathrin Schumann, Kole T Roybal, Rachel E Gate, Chun J Ye, Wendell A Lim, Alexander Marson
Immunotherapies with chimeric antigen receptor (CAR) T cells and checkpoint inhibitors (including antibodies that antagonize programmed cell death protein 1 [PD-1]) have both opened new avenues for cancer treatment, but the clinical potential of combined disruption of inhibitory checkpoints and CAR T cell therapy remains incompletely explored. Here we show that programmed death ligand 1 (PD-L1) expression on tumor cells can render human CAR T cells (anti-CD19 4-1BBζ) hypo-functional, resulting in impaired tumor clearance in a sub-cutaneous xenograft model...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28376571/immunotherapy-of-cancer
#18
Joseph A Trapani, Phillip K Darcy
BACKGROUND: For 50 years, cancer physicians have relied on just three primary treatment modalities: surgery, radiation therapy and chemotherapy. Over that time, enormous progress has been made in understanding cancer biology, targeted anti-cancer drugs have emerged, and thousands of clinical trials have taught us how best to craft treatment combinations that improve clinical outcomes. Only five years ago, a fourth and radically different form of therapy finally emerged: immune‑based cancer therapies...
2017: Australian Family Physician
https://www.readbyqxmd.com/read/28366766/phase-i-escalating-dose-trial-of-car-t-therapy-targeting-cea-metastatic-colorectal-cancers
#19
Chengcheng Zhang, Zhe Wang, Zhi Yang, Meiling Wang, Shiqi Li, Yunyan Li, Rui Zhang, Zhouxing Xiong, Zhihao Wei, Junjie Shen, Yongli Luo, Qianzhen Zhang, Limei Liu, Hong Qin, Wei Liu, Feng Wu, Wei Chen, Feng Pan, Xianquan Zhang, Ping Bie, Houjie Liang, Gabriele Pecher, Cheng Qian
Chimeric antigen receptor T (CAR-T) cells have shown promising efficacy in treatment of hematological malignancies, but its applications in solid tumors need further exploration. In this study, we investigated CAR-T therapy targeting carcino-embryonic antigen (CEA)-positive colorectal cancer (CRC) patients with metastases to evaluate its safety and efficacy. Five escalating dose levels (DLs) (1 × 10(5) to 1 × 10(8)/CAR(+)/kg cells) of CAR-T were applied in 10 CRC patients. Our data showed that severe adverse events related to CAR-T therapy were not observed...
March 30, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28357916/chimeric-antigen-receptor-engineered-stem-cells-a-novel-hiv-therapy
#20
Anjie Zhen, Mayra A Carrillo, Scott G Kitchen
Despite the success of combination antiretroviral therapy (cART) for suppressing HIV and improving patients' quality of life, HIV persists in cART-treated patients and remains an incurable disease. Financial burdens and health consequences of lifelong cART treatment call for novel HIV therapies that result in a permanent cure. Cellular immunity is central in controlling HIV replication. However, HIV adopts numerous strategies to evade immune surveillance. Engineered immunity via genetic manipulation could offer a functional cure by generating cells that have enhanced antiviral activity and are resistant to HIV infection...
March 2017: Immunotherapy
keyword
keyword
101133
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"