Monoclonal antibodies and superantigens: a novel therapeutic approach.
We have developed a monoclonal antibody (mAb) based therapy intended for the treatment of solid tumors utilizing both main arms of the immune system by incorporating the colon carcinoma recognizing mAb C215 and the T cell activating bacterial staphylococcal enterotoxin A (SEA) in a single hybrid molecule. The recombinant tumor specific superantigen C215-SEA retained excellent antigen binding properties while the binding to MHC class II was markedly reduced and should allow targeting of a large fraction of T cells to tumors in vivo. C215-SEA mediated T cell killing of C215 expressing tumor cells irrespective of their expression of MHC class II antigens and induced levels of IFN-gamma and TNF in mononuclear cells sufficient to completely suppress the growth of colon carcinoma cells in vitro. In initial studies of anti-tumor effects, C215Fab-SEA was found to markedly inhibit the growth of colon carcinoma cells transplanted to Scid mice adoptively transferred with human mononuclear cells.
Kalland
T
T
Kabi Pharmacia Oncology, Lund, Sweden.
Dohlsten
M
M
Lind
P
P
Sundstedt
A
A
Abrahmsén
L
L
Hedlund
G
G
Björk
P
P
Lando
P A
PA
Björklund
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy*; D016207:Cytokines / Q000187:drug effects; D004768:Enterotoxins / Q000276:immunology*; D006801:Humans; D007369:Interferon Inducers / Q000276:immunology*; D008213:Lymphocyte Activation; D011994:Recombinant Proteins / Q000627:therapeutic use; D018089:Superantigens / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D016207:Cytokines; D004768:Enterotoxins; D007369:Interferon Inducers; D011994:Recombinant Proteins; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal