Cytotoxic activity of ricin A chain immunotoxins recognising cluster 1, w4 and 5A antigens associated with human small cell lung cancer.
The potential of mouse monoclonal antibodies raised against the human small cell lung cancer (SCLC) cell line SW2 to form active immunotoxins was evaluated using an indirect assay of immunotoxin cytotoxicity. Monoclonal antibodies recognising different SCLC-associated antigens, designated as cluster w4 and cluster 5A antibodies by the First International Workshop on SCLC Antigens, mediated the cytotoxic action of a screening agent made by linking ricin A chain to sheep anti-mouse IgG Fab' fragment. In contrast, monoclonal antibodies belonging to cluster 1 gave no significant cytotoxic effects in conjunction with the screening agent. Immunotoxins made by the direct chemical conjugation of ricin A chain to SWA11 (cluster w4) and SWA20 (cluster 5A) both exhibited selective toxic effects upon the SW2 cell line in tissue culture, inhibiting the incorporation of 3H-leucine by 50% at a concentration (IC50) of approximately 3 x 10(-10) M. An immunotoxin made with SEN36 (cluster 1) was much less potent with an IC50 greater than 1 x 10(-8) M.
Wawrzynczak
E J
EJ
Drug Targeting Laboratory, Institute of Cancer Research, Sutton, Surrey, UK.
Derbyshire
E J
EJ
Henry
R V
RV
Parnell
G D
GD
Smith
A
A
Waibel
R
R
Stahel
R A
RA
D000911:Antibodies, Monoclonal / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000276:immunology; D018288:Carcinoma, Small Cell / Q000276:immunology / Q000628:therapy*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007167:Immunotherapy; D000922:Immunotoxins / Q000627:therapeutic use*; D012276:Ricin / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000922:Immunotoxins; D012276:Ricin