Article: article from journal or magazin.
Allorestricted T lymphocytes with a high avidity T-cell receptor towards NY-ESO-1 have potent anti-tumor activity.
International journal of cancer. Journal international du cancer
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
The cancer-testis antigen NY-ESO-1 has been targeted as a tumor-associated antigen by immunotherapeutical strategies, such as cancer vaccines. The prerequisite for a T-cell-based therapy is the induction of T cells capable of recognizing the NY-ESO-1-expressing tumor cells. In this study, we generated human T lymphocytes directed against the immunodominant NY-ESO-1(157-165) epitope known to be naturally presented with HLA-A*0201. We succeeded to isolate autorestricted and allorestricted T lymphocytes with low, intermediate or high avidity TCRs against the NY-ESO-1 peptide. The avidity of the established CTL populations correlated with their capacity of lysing HLA-A2-positive, NY-ESO-1-expressing tumor cell lines derived from different origins, e.g. melanoma and myeloma. The allorestricted NY-ESO-1-specific T lymphocytes displayed TCRs with the highest avidity and best anti-tumor recognition activity. TCRs derived from allorestricted, NY-ESO-1-specific T cells may be useful reagents for redirecting primary T cells by TCR gene transfer and, therefore, may facilitate the development of adoptive transfer regimens based on TCR-transduced T cells for the treatment of NY-ESO-1-expressing hematological malignancies and solid tumors.
Antibody-Dependent Cell Cytotoxicity, Antigen Presentation, Antigens, Neoplasm/immunology, Cytotoxicity Tests, Immunologic, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Genes, T-Cell Receptor, HLA-A Antigens/immunology, Humans, Membrane Proteins/immunology, Neoplasm Proteins/immunology, Peptide Fragments/immunology, Protein Multimerization, Receptors, Antigen, T-Cell/immunology, T-Lymphocytes, Cytotoxic/immunology
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