A Metabolism Toolbox for CAR T Therapy

A Metabolism Toolbox for CAR T Therapy Xuequn Xu†, J. N. Rashida Gnanaprakasam†, John Sherman† and Ruoning Wang* Center for Childhood Cancer and Blood Diseases, Hematology/Oncology &BMT, The Research Institute at Nationwide Children's Hospital, Ohio State University, Columbus, OH, United States The adoptive transfer of T cells expressing chimeric antigen receptors (CARs) through genetic engineering is one of the most promising new therapies for treating cancer patients. A robust CAR T cell-mediated anti-tumor response requires the coordination of nutrient and energy supplies with CAR T cell expansion and function. However, the high metabolic demands of tumor cells compromise the function of CAR T cells by competing for nutrients within the tumor microenvironment (TME). To substantially improve clinical outcomes of CAR T immunotherapy while treating solid tumors, it is essential to metabolically prepare CAR T cells to overcome the metabolic barriers imposed by the TME. In this review, we discuss a potential metabolism toolbox to improve the metabolic fitness of CAR T cells and maximize the efficacy of CAR T therapy. Cancer Cell Metabolic Program Since cancer cells must constantly proliferate, they must also continuously generate new biomass. This in turn requires a substantially different metabolic program than that of non-proliferating somatic cells. Most non-proliferating cells utilize oxidative phosphorylation (OXPHOS) to ef...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research

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In conclusion, this review reported that IL-37 has a crucial role in reducing infection-associated inflammation and has a good impact on inflammation-induced pathology. However, tight regulation that achieved balance between effector immune responses that required for pathogen elimination and limited tissue damage that resulted from excessive inflammation should be existed in the potential IL-37 therapy to prevent clinical complications of a disease. PMID: 31633447 [PubMed - as supplied by publisher]
Source: International Reviews of Immunology - Category: Allergy & Immunology Tags: Int Rev Immunol Source Type: research
Date: Monday, 10 28, 2019; Speaker: Xiangbo Ruan, Regulation of systemic lipid metabolism by human lncRNAs, The Cao group, CB, NHLBI; Ranganath Muniyappa, Hyperuricemia in insulin resistance, DEOB, NIDDK; Building: Building 10 (Clinical Center); Solarium Conference Room 9S233 (old Bunim Room)
Source: NIH Calendar of Events - Category: American Health Source Type: events
Date: Wednesday, 10 30, 2019; Speaker: Hyunsoo Shawn Je, Prof., Duke-NUS Medical School; Building: Building 5; 127
Source: NIH Calendar of Events - Category: American Health Source Type: events
Date: Tuesday, 11 12, 2019; Speaker: Meira Epplein, PhD, Associate Professor in Population Health Sciences, Associate Prof in Medicine, Department of Medicine, Duke University School of Medicine ; http://epi.grants.cancer.gov/events/infectious-age
Source: NIH Calendar of Events - Category: American Health Source Type: events
Conclusions: The results indicate that a possible mechanism behind an anastomotic leakage is an impaired circulation and thus insufficient saturation to the small intestine peroperatively. This develops into an inflammation both intraperitoneally and intravenously, which, if not reversed, spread within the gastrointestinal tract .The colorectal anastomosis is the most vulnerable part of the gastrointestinal tract postoperatively and hypoxia and inflammation may occur there, and an anastomosis leakage will be the consequence. PMID: 31630578 [PubMed - as supplied by publisher]
Source: Scandinavian Journal of Gastroenterology - Category: Gastroenterology Tags: Scand J Gastroenterol Source Type: research
Publication date: Available online 22 October 2019Source: Stem Cell ResearchAuthor(s): Jonathan Arias-Fuenzalida, Jingwei Yu, Likun Du, Joaquin Custodio, Luigi D. Notarangelo, Lennart Hammarström, Qiang Pan-HammarströmAbstractSelective immunoglobulin-A deficiency (IgAD) is the most common primary immunodeficiency (PID) in the Western world and results in higher susceptibility to infections, autoimmune disorders and malignancies. We generated human induced pluripotent stem cell lines from two patients with selective immunoglobulin-A primary immunodeficiency, PHAi001 and PHAi002. Patient samples were reprogrammed u...
Source: Stem Cell Research - Category: Stem Cells Source Type: research
Publication date: Available online 21 October 2019Source: Stem Cell ResearchAuthor(s): T.A. Shnaider, I.E. Pristyazhnyuk, A.G. Menzorov, N.M. Matveeva, A.A Khabarova, N.A. Skryabin, A.A. Kashevarova, M.E. Lopatkina, L.P. Nazarenko, I.N. Lebedev, O.L. SerovAbstractThe human induced pluripotent stem cell (iPSC) lines, ICGi009-A, ICGi009-B, ICGi013-A and ICGi013-B, were generated from skin fibroblasts of two siblings with intellectual disability. Both patients were carriers of CNTN6 gene microdeletion(Kashevarova et al., 2014). iPSC lines have normal karyotype, express pluripotency markers, are able to differentiate in vitro ...
Source: Stem Cell Research - Category: Stem Cells Source Type: research
Publication date: Available online 21 October 2019Source: Stem Cell ResearchAuthor(s): Haiyan Zhang, Yanyan Ma, Shujuan Yu, Xiaomeng Yang, Yue Li, Jingyun Guan, Rui Dong, Zhongtao Gai, Yi LiuAbstractWe established an induced pluripotent stem cell (iPSC) line (SDQLCHi010-A) from peripheral blood mononuclear cells isolated from a 4-year-old boy with optic nerve malformation and intellectual disability carrying a heterozygous mutation (c.220A>G (p.S74G)) in PAX6 gene. Non-integrating episomal vectors containing OCT4, SOX2, KLF4, BCL-XL and MYC were used for reprogramming. The established iPSC line showed normal karyotype, ...
Source: Stem Cell Research - Category: Stem Cells Source Type: research
Publication date: Available online 21 October 2019Source: Stem Cell ResearchAuthor(s): Chanchao Lorthongpanich, Nittaya Jiamvoraphong, Prapasri Supakun, Nattaya Damkham, Papussorn Terbto, Supaporn Waeteekul, Yaowalak U-pratya, Chuti Laowtammathron, Surapol IssaragrisilAbstractWWTR1 or TAZ (WWTR1/TAZ) is a transcriptional coactivator that acts as a downstream regulatory target in the Hippo signaling pathway, which plays a pivotal role in regulating cell proliferation and anti-apoptosis. It has been shown in other cell types that WWTR1/TAZ plays a redundant role to its homolog YAP1. Using CRISPR/Cas9 gene editing, we establi...
Source: Stem Cell Research - Category: Stem Cells Source Type: research
Publication date: Available online 21 October 2019Source: Stem Cell ResearchAuthor(s): Gabriele Louise Soares Martins, Bruno Diaz Paredes, Gabriela Louise de Almeida Sampaio, Carolina Kymie Vasques Nonaka, Katia Nunes da Silva, Kyan James Allahdadi, Milena Botelho Pereira Soares, Ricardo Ribeiro dos Santos, Bruno Solano de Freitas SouzaAbstractHuman-induced pluripotent stem cell (hiPSC) CBTCi001-A line was generated from a healthy 30-year old male dermal fibroblasts using non-integrative reprogramming method using episomal-based plasmids expressing OCT4, SOX2, KLF4, and MYCL. Characterization of CBTCi001-A was confirmed by...
Source: Stem Cell Research - Category: Stem Cells Source Type: research
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