TITLE

Molecular insights for optimizing T cell receptor specificity against cancer

AUTHOR(S)
Hebeisen, Michael; Oberle, Susanne; Presotto, Danilo; Speiser, Daniel E.; Zehn, Dietmar; Rufer, Nathalie
PUB. DATE
June 2013
SOURCE
Frontiers in Immunology;Jun2013, Vol. 4, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Cytotoxic CD8 T cells mediate immunity to pathogens and they are able to eliminate malignant cells. Immunity to viruses and bacteria primarily involves CD8 T cells bearing high affinity T cell receptors (TCRs), which are specific to pathogen derived (non-self) antigens. Given the thorough elimination of high affinity self/tumor-antigen reactive T cells by central and peripheral tolerance mechanisms, anti-cancer immunity mostly depends on TCRs with intermediate-to-low affinity for self-antigens. Because of this, a promising novel therapeutic approach to increase the efficacy of tumorreactive T cells is to engineer their TCRs, with the aim to enhance their binding kinetics to pMHC complexes, or to directly manipulate the TCR signaling cascades. Such manipulations require a detailed knowledge on how pMHC-TCR and coreceptors binding kinetics impact the T cell response. In this review, we present the current knowledge in this field. We discuss future challenges in identifying and targeting the molecular mechanisms to enhance the function of natural or TCRaffinity optimized T cells, and we provide perspectives for the development of protective anti-tumor T cell responses
ACCESSION #
88031822

 

Related Articles

  • High-throughput identification of antigen-specific TCRs by TCR gene capture. Linnemann, Carsten; Heemskerk, Bianca; Kvistborg, Pia; Kluin, Roelof J C; Bolotin, Dmitriy A; Chen, Xiaojing; Bresser, Kaspar; Nieuwland, Marja; Schotte, Remko; Michels, Samira; Gomez-Eerland, Raquel; Jahn, Lorenz; Hombrink, Pleun; Legrand, Nicolas; Shu, Chengyi Jenny; Mamedov, Ilgar Z; Velds, Arno; Blank, Christian U; Haanen, John B A G; Turchaninova, Maria A // Nature Medicine;Nov2013, Vol. 19 Issue 11, p1534 

    The transfer of T cell receptor (TCR) genes into patient T cells is a promising approach for the treatment of both viral infections and cancer. Although efficient methods exist to identify antibodies for the treatment of these diseases, comparable strategies to identify TCRs have been lacking....

  • Cellular receptor for pixuna virus in chicken embryonic fibroblasts. Paglini, G.; del C.Pereyra, E.; Paglini, S. // Medical Microbiology & Immunology;Jun2006, Vol. 195 Issue 2, p85 

    In this study, we describe the isolation and partial characterization of a Pixuna virus receptor, which is a component of a plasma membrane fraction of chicken embryo fibroblast (CEF). Polyclonal antiserum was prepared from rabbits immunized with the membrane fraction. Said polyclonal antiserum...

  • Using Modified Antigenic Sequences to Develop Cancer Vaccines: Are We Losing the Focus? Valmori, Danila; Ayyoub, Maha // PLoS Medicine;Nov2004, Vol. 1 Issue 2, p111 

    Comments on the use of modified antigenic sequences in the development of cancer vaccines. Significance of alteration in the major histocompatibility complex class molecules to T cell receptors; Role of heteroclitic tumor antigen peptides in the improvement of immune response; Background on the...

  • Primer sets for cloning the human repertoire of T cell Receptor Variable regions. Boria, Ilenia; Cotella, Diego; Dianzani, Irma; Santoro, Claudio; Sblattero, Daniele // BMC Immunology;2008, Vol. 9, Special section p1 

    Background: Amplification and cloning of naïve T cell Receptor (TR) repertoires or antigen-specific TR is crucial to shape immune response and to develop immuno-based therapies. TR variable (V) regions are encoded by several genes that recombine during T cell development. The cloning of...

  • Effective adoptive therapy of tap-deficient lymphoma using diverse high avidity alloreactive T cells. Popmihajlov, Zoran; Santori, Fabio R.; Gebreselassie, Daniel; Sandler, Anthony D.; Vukmanovic, Stanislav // Cancer Immunology, Immunotherapy;Apr2010, Vol. 59 Issue 4, p629 

    High avidity for antigen and diversity of T cell receptor (TCR) repertoire are essential for effective immunity against cancer. We have previously created a transgenic mouse strain with increased TCR avidity in a diverse T cell population. In this report, we show that strong alloreactive...

  • T-cell clonotypes in cancer. thor Straten, Per; Schrama, David; Andersen, Mads Hald; Becker, Jürgen C. // Journal of Translational Medicine;2004, Vol. 2, p11 

    Cells of the immune system spontaneously recognize autologous tumor cells and T cells are believed to be the main effector cells for the immune surveillance of cancer. Recent advances in our understanding of basic and tumor immunology together with methodological developments implies that tumor...

  • Clonal expansions of CD8 T cells in latently HSV-1-infected human trigeminal ganglia. Held, Kathrin; Eiglmeier, Ingrid; Himmelein, Susanne; Sinicina, Inga; Brandt, Thomas; Theil, Diethilde; Dornmair, Klaus; Derfuss, Tobias // Journal of NeuroVirology;Feb2012, Vol. 18 Issue 1, p62 

    Herpes simplex virus type 1 latency in trigeminal ganglia (TG) is accompanied by a chronic immune cell infiltration. The aim of this study was to analyse the T-cell receptor �-chain repertoire in latently HSV-1 infected human TG. Using complementarity-determining region 3 spectratyping, 74...

  • Dual receptor T cells extend the immune repertoire for foreign antigens. He, Xin; Janeway, Charles A.; Levine, Matthew; Robinson, Eve; Preston-Hurlburt, Paula; Viret, Christophe; Bottomly, Kim // Nature Immunology;Feb2002, Vol. 3 Issue 2, p127 

    Since the discovery of T cells that express two T cell receptors (TCRs), termed dual TCR cells, most studies have focused on their autoimmune potential, while their beneficial roles remained elusive. We identified, in normal mice, dual TCR cells that participated in the immune response to a...

  • Antigen magnetism. Ahmad, Sharon // Nature Reviews Immunology;Nov2006, Vol. 6 Issue 11, p797 

    The article examines the role of antigen in the survival of CD8+ T cells during chronic viral infection. A study was conducted on polyomavirus infected mice induced with partial haematopoietic chimerism. The results detected the presence of both host and donor virus-specific CD8+ T cells in...

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