Allorestricted T lymphocytes with a high avidity T-cell receptor towards NY-ESO-1 have potent anti-tumor activity.
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.
Krönig
Holger
H
Department of Hematology/Oncology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
Hofer
Kathrin
K
Conrad
Heinke
H
Guilaume
Philippe
P
Müller
Julia
J
Schiemann
Matthias
M
Lennerz
Volker
V
Cosma
Antonio
A
Peschel
Christian
C
Busch
Dirk H
DH
Romero
Pedro
P
Bernhard
Helga
H
D000920:Antibody-Dependent Cell Cytotoxicity; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D019672:Genes, T-Cell Receptor; D015234:HLA-A Antigens / Q000276:immunology*; D015789:HLA-A2 Antigen; D006801:Humans; D008565:Membrane Proteins / Q000276:immunology*; D009363:Neoplasm Proteins / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D055503:Protein Multimerization; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; C504237:peptide NY-ESO-1 157-165