TITLE

Young T cells age during a redirected anti-tumor attack: chimeric antigen receptor-provided dual costimulation is half the battle

AUTHOR(S)
Hombach, Andreas A.; Abken, Hinrich
PUB. DATE
June 2013
SOURCE
Frontiers in Immunology;Jun2013, Vol. 4, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Adoptive therapy with chimeric antigen receptor (CAR)-redirected T cells showed spectacular efficacy in the treatment of leukemia in recent early phase trials. Patient's T cells were ex vivo genetically engineered with a CAR, amplified and re-administered to the patient. While T cells mediating the primary response were predominantly of young effector and central memory phenotype, repetitive antigen engagement irreversible triggers T cell maturation leaving late memory cells with the KLRG1+ CD57+ CD7- CCR7- phenotype in the long-term. These cells preferentially accumulate in the periphery, are hypo-responsive uponTCR engagement and prone to activation-induced cell death. A recent report indicates that those T cells can be rescued by CAR provided CD28 and OX40 (CD134) stimulation. We discuss the strategy with respect to prolong the anti-tumor response and to improve the over-all efficacy of adoptive cell therapy
ACCESSION #
88031828

 

Related Articles

  • B7H6-specific chimeric antigen receptors lead to tumor elimination and host antitumor immunity. Wu, M-R; Zhang, T; DeMars, L R; Sentman, C L // Gene Therapy;Aug2015, Vol. 22 Issue 8, p675 

    Chimeric antigen receptor (CAR) T-cell therapies have demonstrated durable and potentially curative therapeutic efficacy against B-cell leukemia in clinical trials. A CAR strategy can target any tumor surface antigens as long as an antigen-binding receptor can be generated. New CARs that target...

  • Selective Inhibition of Tumor Growth by Clonal NK Cells Expressing an ErbB2/HER2-Specific Chimeric Antigen Receptor. Schönfeld, Kurt; Sahm, Christiane; Zhang, Congcong; Brendel, Christian; Köhler, Sylvia; Grez, Manuel; Rieger, Michael A; Wels, Winfried S; Naundorf, Sonja; Kühlcke, Klaus; Odendahl, Marcus; Tonn, Torsten; Nowakowska, Paulina; Bönig, Halvard; Seifried, Erhard; Köhl, Ulrike; Kloess, Stephan; Holtgreve-Grez, Heidi; Jauch, Anna; Schmidt, Manfred // Molecular Therapy;Feb2015, Vol. 23 Issue 2, p330 

    Natural killer (NK) cells are an important effector cell type for adoptive cancer immunotherapy. Similar to T cells, NK cells can be modified to express chimeric antigen receptors (CARs) to enhance antitumor activity, but experience with CAR-engineered NK cells and their clinical development is...

  • Advances in Assay Technologies for CAR T-Cell Therapies. Armstrong, Alison // BioPharm International;Feb2016, Vol. 29 Issue 2, p32 

    The article discusses the advances in assay technologies for chimeric antigen receptor modified T-cells (CAR-T) therapies. Topics include the schematic of the manufacturing process and associated testing regimes for cell therapy production, guidelines for the production and testing of cell-based...

  • Massive apoptotic cell death of human glioma cells via a mitochondrial pathway following 5-aminolevulinic acid-mediated photodynamic therapy. Hiroto Inoue; Yoshinaga Kajimoto; Masa-Aki Shibata; Norio Miyoshi; Naoko Ogawa; Shin-Ichi Miyatake; Yoshinori Otsuki; Toshihiko Kuroiwa // Journal of Neuro-Oncology;Jul2007, Vol. 83 Issue 3, p223 

    Abstract  The basic mechanism of cell death induced by 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT) (ALA-PDT) in glioma cells has not been fully elucidated. In this study, the details of the cell death mechanism induced by ALA-PDT were investigated in three...

  • Induction of immunogenic cell death by targeting RIG-I-like helicases in pancreatic cancer. Schnurr, Max; Duewell, Peter // OncoImmunology;Sep2014, Vol. 3 Issue 9, pN.PAG 

    RIG-I-like helicases (RLH) are cytosolic sensors for viral RNA inducing type I interferon production. We found that pancreatic cancer cells express functional RLH and are susceptible to RLH-induced apoptosis via intrinsic and extrinsic pathways. Tumor cells displayed features of immunogenic cell...

  • Therapeutic targeting of naturally presented myeloperoxidase-derived HLA peptide ligands on myeloid leukemia cells by TCR-transgenic T cells. Klar, R; Schober, S; Rami, M; Mall, S; Merl, J; Hauck, S M; Ueffing, M; Admon, A; Slotta-Huspenina, J; Schwaiger, M; Stevanović, S; Oostendorp, R A J; Busch, D H; Peschel, C; Krackhardt, A M // Leukemia (08876924);Dec2014, Vol. 28 Issue 12, p2355 

    T cells have been proven to be therapeutically effective in patients with relapsed leukemias, although target antigens on leukemic cells as well as T-cell receptors (TCRs), potentially recognizing those antigens, are mostly unknown. We have applied an immunopeptidomic approach and isolated human...

  • Gamida Cell Closes $10 Mln E Financing Round Earmarked to Support Global.  // Biomedical Market Newsletter;5/18/2012, Vol. 21, p1 

    The article reports that Gamida Cell Ltd. has ended its 10 million dollar financing round in which all the shareholders had participated. It mentions that the funding will be utilized in several methods of commercialization of product of the company including treatment of blood cancer, cell...

  • RB and RB2/p130 genes demonstrate both specific and overlapping functions during the early steps of in vitro neural differentiation of marrow stromal stem cells. Jori, F. P.; Melone, M. A. B; Napolitano, M. A.; Cipollaro, M.; Cascino, A.; Giordano, A.; Galderisi, U. // Cell Death & Differentiation;Jan2005, Vol. 12 Issue 1, p65 

    Marrow stromal stem cells (MSCs) are stem-like cells that are currently being tested for their potential use in cell therapy for a number of human diseases. MSCs can differentiate into both mesenchymal and nonmesenchymal lineages. In fact, in addition to bone, cartilage and fat, it has been...

  • Ectopic Expression of E2F1 Stimulates β-Cell Proliferation and Function. Grouwels, Gael; Ying Cai; Hoebeke, Inge; Leuckx, Gunter; Heremans, Yves; Ziebold, Ulrike; Stangé, Geert; Chintinne, Marie; Zhidong Ling; Pipeleers, Daniel; Heimberg, Harry; Van de Casteele, Mark // Diabetes;Jun2010, Vol. 59 Issue 6, p1435 

    OBJECTIVE--Generating functional β-cells by inducing their proliferation may provide new perspectives for cell therapy in diabetes. Transcription factor E2F1 controls G[sub 1]- to S-phase transition during the cycling of many cell types and is required for pancreatic β-cell growth and...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics