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chimeric receptor

Xingliang Guo, Hua Jiang, Bizhi Shi, Min Zhou, Honghong Zhang, Zhimin Shi, Guoxiu Du, Hong Luo, Xiuqi Wu, Yi Wang, Ruixin Sun, Zonghai Li
Cancer immunotherapy has made unprecedented breakthrough in the fields of chimeric antigen receptor-redirected T (CAR T) cell therapy and immune modulation. Combination of CAR modification and the disruption of endogenous inhibitory immune checkpoints on T cells represent a promising immunotherapeutic modality for cancer treatment. However, the potential for the treatment of hepatocellular carcinoma (HCC) has not been explored. In this study, the gene expressing the programmed death 1 receptor (PD-1) on the Glypican-3 (GPC3)-targeted second-generation CAR T cells employing CD28 as the co-stimulatory domain was disrupted using the CRISPR/Cas9 gene-editing system...
2018: Frontiers in Pharmacology
Inmaculada Hernandez, Vinay Prasad, Walid F Gellad
No abstract text is available yet for this article.
October 11, 2018: JAMA Oncology
Melanie D Whittington, Daniel A Ollendorf, Jonathan D Campbell
No abstract text is available yet for this article.
October 11, 2018: JAMA Oncology
Si Lin Koo, Who Whong Wang, Han Chong Toh
In recent years, the impressive number of cancer immunotherapy drugs approved has been unprecedented-building on over a century of understanding on how the immune system combats cancer, and how cancer evades it. Leading the charge are the immune checkpoint inhibitor monoclonal antibodies, and adoptive cell therapy with chimeric- antigen-receptor (CAR)-T cell therapy. These breakthrough therapies have led to improved survival in patients with many advanced cancers. Some of the clinical outcomes have been striking, and may even be potentially curative in some terminal cancer patients...
September 2018: Annals of the Academy of Medicine, Singapore
Wei Zhang, Kimberly R Jordan, Brian Schulte, Enkhtsetseg Purev
Background: Chimeric antigen receptor (CAR) T-cell therapy is highly effective for treating acute lymphoblastic leukemia and non-Hodgkin's lymphoma with high rate complete responses. However, the broad clinical application of CAR T-cell therapy has been challenging, largely due to the lack of widespread ability to produce and high cost of CAR T-cell products using traditional methods of production. Automated cell processing in a closed system has emerged as a potential method to increase the feasibility of producing CAR T cells locally at academic centers due to its minimal reliance on experienced labor, thereby making the process less expensive and more consistent than traditional methods of production...
2018: Drug Design, Development and Therapy
Xia Xiao, Xiaoyuan He, Qing Li, Huan Zhang, Juanxia Meng, Yanyu Jiang, Qi Deng, Mingfeng Zhao
BACKGROUND: Tumor immunotherapy with chimeric antigen receptor T cells (CAR-T) is a promising new treatment for B-cell malignancies and has produced exciting results. However, cytokine release syndrome (CRS) is the most significant toxicity associated with this treatment and can be life-threatening. CASE PRESENTATION: A 23-year-old male patient had been diagnosed with relapsed and refractory B-cell acute lymphocytic leukemia. The patient was recruited into our CAR-T clinical trial, and 1×106 /kg of engineered anti-CD19 CAR-T cells was administered...
October 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Federica Costa, Rituparna Das, Jithendra Kini Bailur, Kavita Dhodapkar, Madhav V Dhodapkar
Despite major improvements in the treatment landscape, most multiple myeloma (MM) patients eventually succumb to the underlying malignancy. Immunotherapy represents an attractive strategy to achieve durable remissions due to its specificity and capacity for long term memory. Activation of immune cells is controlled by a balance of agonistic and inhibitory signals via surface and intracellular receptors. Blockade of such inhibitory immune receptors (termed as "immune checkpoints") including PD-1/PD-L1 has led to impressive tumor regressions in several cancers...
2018: Frontiers in Immunology
Mehmet Akce, Mohammad Y Zaidi, Edmund K Waller, Bassel F El-Rayes, Gregory B Lesinski
Pancreatic cancer has a dismal prognosis and effective treatment options are limited. It is projected to be the second most common cause of cancer related mortality in the United States by 2030 and there is urgent unmet need for novel systemic treatment options. Immunotherapy with antibodies targeting PD-1, PD-L1, CTLA-4 has not shown clinical activity in unselected pancreatic cancer, emphasizing the need for combination immunotherapy approaches or other therapeutic strategies. As such, chimeric antigen receptor (CAR) T cell therapy represents an emerging therapeutic option for pancreatic cancer...
2018: Frontiers in Immunology
Dongmei Wang, Rui Shi, Qinglong Wang, Jianqiang Li
Philadelphia chromosome-positive (Ph-positive) acute leukemia (ALL) accounts for around one quarter of adult cases of ALL and is usually associated with poor prognosis. The patients still encounter a high rate of relapse even after they receive hematopoietic stem cell transplantation (HSCT). HSCT is considered the established therapy and best option for many malignant ALL cases, however, disease relapse remains the main reason of failure. In recent years, chimeric antigen receptor (CAR) T-cell therapy has become a promising treatment for patients with advanced blood cancers...
2018: OncoTargets and Therapy
Hamid Reza Mirzaei, Hamed Mirzaei, Afshin Namdar, Majid Rahmati, Brian G Till, Jamshid Hadjati
The adoptive transfer of genetically engineered T cells modified to express a chimeric antigen receptor (CAR) has shown remarkable activity and induces long-term remissions in patients with advanced hematologic malignancies. To date, little is known about predictive indicators of therapeutic efficacy or serious toxicity after CAR T-cell therapy in clinical practice. Biomarkers are not only potentially able to inform physicians and researchers of immunotherapy targets in particular but could also be used to monitor the effectiveness of treatments and to predict incidence of side effects in some circumstances...
October 14, 2018: Journal of Cellular Physiology
Paola Ghione, Alison J Moskowitz, Nadia E K De Paola, Steven M Horwitz, Marco Ruella
PURPOSE OF REVIEW: Novel immunotherapies such as checkpoint inhibitors, bispecific antibodies, and chimeric antigen receptor T cells are leading to promising responses when treating solid tumors and hematological malignancies. T cell neoplasms include leukemia and lymphomas that are derived from T cells and overall are characterized by poor clinical outcomes. This review describes the rational and preliminary results of immunotherapy for patients with T cell lymphoma and leukemia. RECENT FINDINGS: For T cell neoplasms, despite significant research effort, only few agents, such as monoclonal antibodies and allogeneic stem cell transplantation, showed some clinical activity...
October 13, 2018: Current Hematologic Malignancy Reports
Syed Ali Haider, Syed Maaz Tariq, Mohammad Hasan
No abstract text is available yet for this article.
September 2018: JPMA. the Journal of the Pakistan Medical Association
Marion Alcantara, Melania Tesio, Carl H June, Roch Houot
Chimeric antigen receptor (CAR) T-cells targeting CD19 demonstrated remarkable efficacy for the treatment of B-cell malignancies. The development of CAR T-cells against T-cell malignancies appears more challenging due to the similarities between the therapeutic, normal and malignant T-cells. The obstacles include CAR T-cell fratricide, T-cell aplasia, and contamination of CAR T-cell products with malignant T-cells. Here, we review these challenges and propose solutions to overcome these limitations.
October 12, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Dusan Hanidziar, Edward Bittner
No abstract text is available yet for this article.
November 2018: Critical Care Medicine
Carlos A Ramos, Rayne Rouce, Catherine S Robertson, Amy Reyna, Neeharika Narala, Gayatri Vyas, Birju Mehta, Huimin Zhang, Olga Dakhova, George Carrum, Rammurti T Kamble, Adrian P Gee, Zhuyong Mei, Meng-Fen Wu, Hao Liu, Bambi Grilley, Cliona M Rooney, Helen E Heslop, Malcolm K Brenner, Barbara Savoldo, Gianpietro Dotti
Second-generation (2G) chimeric antigen receptors (CARs) targeting CD19 are highly active against B cell malignancies, but it is unknown whether any of the costimulatory domains incorporated in the CAR have superior activity to others. Because CD28 and 4-1BB signaling activate different pathways, combining them in a single third-generation (3G) CAR may overcome the limitations of each individual costimulatory domain. We designed a clinical trial in which two autologous CD19-specific CAR-transduced T cell products (CD19...
September 13, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Sergey N Zolov, Skyler P Rietberg, Challice L Bonifant
Targeted adoptive immunotherapy with engineered T cells is a promising treatment for refractory hematologic malignancies. However, many patients achieving early complete remissions ultimately relapse. Immunosuppressive ligands are expressed on tumor and supportive cells in the tumor microenvironment (TME). When activated, T cells express associated "checkpoint" receptors. Binding of co-inhibitory ligands and receptors may directly contribute to T-cell functional exhaustion. It is not known whether all T cells engineered to express chimeric antigen receptors (CARs) are subject to checkpoint-mediated regulation...
October 8, 2018: Cytotherapy
Yibo Yin, Alina C Boesteanu, Zev A Binder, Chong Xu, Reiss A Reid, Jesse L Rodriguez, Danielle R Cook, Radhika Thokala, Kristin Blouch, Bevin McGettigan-Croce, Logan Zhang, Christoph Konradt, Alexandria P Cogdill, M Kazim Panjwani, Shuguang Jiang, Denis Migliorini, Nadia Dahmane, Avery D Posey, Carl H June, Nicola J Mason, Zhiguo Lin, Donald M O'Rourke, Laura A Johnson
We generated two humanized interleukin-13 receptor α2 (IL-13Rα2) chimeric antigen receptors (CARs), Hu07BBz and Hu08BBz, that recognized human IL-13Rα2, but not IL-13Rα1. Hu08BBz also recognized canine IL-13Rα2. Both of these CAR T cell constructs demonstrated superior tumor inhibitory effects in a subcutaneous xenograft model of human glioma compared with a humanized EGFRvIII CAR T construct used in a recent phase 1 clinical trial ( NCT02209376). The Hu08BBz demonstrated a 75% reduction in orthotopic tumor growth using low-dose CAR T cell infusion...
December 21, 2018: Molecular Therapy Oncolytics
Sandro Matosevic
Natural killer (NK) cells are powerful immune effectors whose antitumor activity is regulated through a sophisticated network of activating and inhibitory receptors. As effectors of cancer immunotherapy, NK cells are attractive as they do not attack healthy self-tissues nor do they induce T cell-driven inflammatory cytokine storm, enabling their use as allogeneic adoptive cellular therapies. Clinical responses to adoptive NK-based immunotherapy have been thwarted, however, by the profound immunosuppression induced by the tumor microenvironment, particularly severe in the context of solid tumors...
2018: Journal of Immunology Research
Sarah Löw, Catherine H Han, Tracy T Batchelor
Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal non-Hodgkin lymphoma (NHL), confined to the brain, eyes, spinal cord or leptomeninges without systemic involvement. Overall prognosis, diagnosis and management of PCNSL differ from other types of NHL. Prompt diagnosis and initiation of treatment are vital to improving clinical outcomes. PCNSL is responsive to radiation therapy, however whole-brain radiotherapy (WBRT) inadequately controls the disease when used alone and its delayed neurotoxicity causes neurocognitive impairment, especially in elderly patients...
2018: Therapeutic Advances in Neurological Disorders
Young-Sun Lee, Myung-Ho Kim, Hyon-Seung Yi, So Yeon Kim, Hee-Hoon Kim, Ji Hoon Kim, Jong Eun Yeon, Kwan Soo Byun, Jin-Seok Byun, Won-Il Jeong
The expression of chemokine receptor CX3 CR1 is related to migration and signaling in cells of the monocyte-macrophage lineage. The precise roles of CX3 CR1 in the liver have been investigated but not clearly elucidated. Here, we investigated the roles of CX3 CR1 in hepatic macrophages and liver injury. Hepatic and splenic CX3 CR1low F4/80low monocytes and CX3 CR1low CD16- monocytes were differentiated into CX3 CR1high F4/80high or CX3 CR1high CD16+ macrophages by co-culture with endothelial cells. Moreover, CX3 CL1 deficiency in human umbilical vein endothelial cells (HUVECs) attenuated the expression of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), whereas recombinant CX3 CL1 treatment reversed this expression in co-cultured monocytes...
October 10, 2018: Scientific Reports
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