Superantigen-induced lysis of melanoma cells.
Superantigens like the Staphylococcus enterotoxin A (SEA) can direct cytotoxic T lymphocytes expressing certain T cell receptor V beta regions to lyse MHC class II-positive target cells. This superantigen-dependent cellular cytotoxicity (SDCC) has been extended to MHC class II-negative tumour cells by targeting T cells via conjugates of a tumour-specific monoclonal antibody (moAb) and a superantigen. In the present study the MHC class II-negative human melanoma cell lines G361 and MaRI were tested for susceptibility to SDCC in vitro. Antibodies recognizing the disialoganglioside GD3 and the CD10 antigen were linked to SEA either by a recombinant protein A-SEA fusion protein or an anti-kappa moAb-SEA chemical conjugate. Specific lysis of melanoma cells was dose- and effector to target (E:T) cell ratio-dependent. Introduction of a point mutation into the SEA gene (producing SEAm9) in order to reduce MHC II affinity of the superantigen, which has already been shown to severely diminish superantigen-dependent binding and lysis of MHC class II-positive cells, did not influence antibody-targeted SDCC. Cytotoxicity was equal with both antibodies (anti-GD3 and anti-CD10) and independent of whether protein A-SEA, protein A-SEAm9 or anti-kappa-SEA were used.
Krull
F
F
Department of Oncology and Hematology, Children's University Hospital, Tübingen, Germany.
Holzer
U
U
Ihle
J
J
Bethge
W
W
Fierlbeck
G
G
Kalland
T
T
Dohlsten
M
M
Niethammer
D
D
Dannecker
G E
GE
D000951:Antigens, Neoplasm / Q000096:biosynthesis; D016923:Cell Death / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004768:Enterotoxins / Q000494:pharmacology*; D005732:Gangliosides / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007369:Interferon Inducers / Q000494:pharmacology*; D008223:Lymphoma / Q000188:drug therapy; D008545:Melanoma / Q000276:immunology / Q000473:pathology*; D011993:Recombinant Fusion Proteins; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology*; D013211:Staphylococcus aureus; D018089:Superantigens / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D004768:Enterotoxins; D005732:Gangliosides; D000949:Histocompatibility Antigens Class II; D007369:Interferon Inducers; D011993:Recombinant Fusion Proteins; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal; C026226:ganglioside, GD3