Characterization of a chimeric T-cell receptor with specificity for the Hodgkin's lymphoma-associated CD30 antigen.
Recombinant receptors with antibody-like specificity for tumor-associated antigens were shown to direct specifically T cells to target tumor cells. Hodgkin and Reed-Sternberg cells, the malignant cell population in Hodgkin's lymphoma, express high amounts of the cell surface antigen CD30. An anti-CD30 T-cell receptor with cellular activation properties is expected to graft T cells with specificity to Hodgkin cells. Here, the authors characterize a chimeric T-cell receptor with an extracellular domain consisting of the single-chain antibody fragment HRS3-scFv with specificity for the CD30 antigen and intracellular domain of the signal transducing part of the Fc-epsilon-I-gamma receptor. The HRS3-scFv was derived from the monoclonal anti-CD30 antibody HRS3 and retained specificity for the CD30 antigen. The recombinant HRS3-scFv-gamma receptor was expressed under control of the RSV-LTR after transfection into MD45 T-cells. The chimeric receptor protein is detected and analyzed by enzyme-linked immunosorbent assay (ELISA) and immunoprecipitation. Expression of the chimeric receptor converts MD45 T cells to specificity for CD30+ lymphoma cells. Specific cross-linking of the chimeric receptor with antigen resulted in cytolytic reactivity against CD30+ tumor cells in vitro. The results demonstrate that the chimeric receptor HRS3-scFv-gamma converts T cells to a specific MHC-unrestricted cytolytic response against CD30+ tumor cells offering an alternative strategy in cellular immunotherapy of Hodgkin's disease.
Hombach
A
A
Klinik I für Innere Medizin, Universität zu Köln, Germany.
Heuser
C
C
Sircar
R
R
Tillmann
T
T
Diehl
V
V
Pohl
C
C
Abken
H
H
D000818:Animals; D000911:Antibodies, Monoclonal; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D015870:Gene Expression; D006689:Hodgkin Disease / Q000276:immunology*; D006801:Humans; D006825:Hybridomas; D007128:Immunoglobulin Fragments / Q000235:genetics / Q000276:immunology; D017730:Ki-1 Antigen / Q000276:immunology*; D051379:Mice; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D013601:T-Lymphocytes; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D007128:Immunoglobulin Fragments; D017730:Ki-1 Antigen; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011993:Recombinant Fusion Proteins; C055966:immunoglobulin Fv