A listing of human tumor antigens recognized by T cells

NCI-Frederick, Фредерик, Maryland, United States
Cancer Immunology and Immunotherapy (Impact Factor: 3.94). 01/2001; 50(1):3-15. DOI: 10.1007/s002620000169
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Available from: Giorgio Parmiani, Oct 06, 2015
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    • "melanocytes) into tumors called melanomas [3] [4]. A third possible source of tumor antigens are proteins normally important for regulating cell growth and survival, that commonly mutate into cancer inducing molecules called oncogenes [1] [5] [6]. "
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    • "Additional TAA, the so called cancer/testis antigens, such as those of the MAGE-A family and NY-ESO-1, are aberrantly expressed in cancer cells of diverse histological origin and in healthy spermatogonia or placental cells. Most importantly, mutated gene products of proven oncogenic relevance may also be recognized as antigens by specific T cells[15] . "
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    ABSTRACT: Interaction between cancer cells and immune system critically affects development, progression and treatment of human malignancies. Experimental animal models and conventional "in vitro" studies have provided a wealth of information on this interaction, currently used to develop immune-mediated therapies. Studies utilizing three-dimensional culture technologies have emphasized that tumor architecture dramatically influences cancer cell-immune system interaction by steering cytokine production and regulating differentiation patterns of myeloid cells, and decreasing the sensitivity of tumor cells to lymphocyte effector functions. Hypoxia and increased production of lactic acid by tumor cells cultured in 3D architectures appear to be mechanistically involved. 3D culture systems could be further developed to (i) include additional cell partners potentially influencing cancer cell-immune system interaction, (ii) enable improved control of hypoxia, and (iii) allow the use of freshly derived clinical cancer specimens. Such advanced models will represent new tools for cancer immunobiology studies and for pre-clinical assessment of innovative treatments.
    Advanced drug delivery reviews 05/2014; 79-80. DOI:10.1016/j.addr.2014.05.003 · 15.04 Impact Factor
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    • "Thus, CD8+ T cells play an important role during viral infections (Miles et al., 2010), which typically elicit strong CD8+ T cell responses, many of which have been well-characterized, including those to HTLV-1 (Bieganowska et al., 1999; Vine et al., 2004), although some viruses can escape CD8+ T cell mediated clearance (Klenerman and Zinkernagel, 1998; Overbaugh and Bangham, 2001). Cancers too, as a result of their malignant transformation, have altered protein expression causing the presentation of tumor-associated peptide antigens (TAPAs) (Renkvist et al., 2001; Cole et al., 2009). However, although these TAPAs can elicit a host CD8+ T cell response, this is often insufficient to cause tumor rejection (Blohm et al., 2002; Parkhurst et al., 2004). "
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    ABSTRACT: Natural T cell receptors (TCRs) generally bind to their cognate pMHC molecules with weak affinity and fast kinetics, limiting their use as therapeutic agents. Using phage display, we have engineered a high affinity version of the A6 wild-type TCR (A6wt), specific for the human leukocyte antigen (HLA-A(∗)0201) complexed with human T cell lymphotropic virus type 111-19 peptide (A2-Tax). Mutations in just 4 residues in the CDR3β loop region of the A6wt TCR were selected that improved binding to A2-Tax by nearly 1000-fold. Biophysical measurements of this mutant TCR (A6c134) demonstrated that the enhanced binding was derived through favorable enthalpy and a slower off-rate. The structure of the free A6c134 TCR and the A6c134/A2-Tax complex revealed a native binding mode, similar to the A6wt/A2-Tax complex. However, concordant with the more favorable binding enthalpy, the A6c134 TCR made increased contacts with the Tax peptide compared with the A6wt/A2-Tax complex, demonstrating a peptide-focused mechanism for the enhanced affinity that directly involved the mutated residues in the A6c134 TCR CDR3β loop. This peptide-focused enhanced TCR binding may represent an important approach for developing antigen specific high affinity TCR reagents for use in T cell based therapies.
    Frontiers in Immunology 06/2013; 4:168. DOI:10.3389/fimmu.2013.00168
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