Selective cytotoxic effects of a ricin A chain immunotoxin made with the monoclonal antibody SWA11 recognising a human small cell lung cancer antigen.
The potential of mouse monoclonal antibodies for recognising different antigens associated with human small cell lung cancer (SCLC) to form active immunotoxins was assessed by an indirect in vitro screening assay. The screening agent used was a conjugate made by linking ricin A chain to a sheep anti-mouse IgG Fab' fragment via a disulphide bond. The monoclonal antibodies SWA11 and SWA20 both mediated the toxic effects of ricin A chain against the HC12 classic SCLC cell line in dose-dependent fashion. The SWA11 antibody was the more effective; in combination with the screening agent at a concentration of 1 x 10(-7) M, it inhibited the incorporation of [3H] leucine into HC12 cells by 94% compared with only 44% inhibition in the case of SWA20. An immunotoxin made by the direct chemical conjugation of ricin A chain to SWA11 exhibited selective toxic effects upon HC12 cells in tissue culture inhibiting the incorporation of [3H] leucine by 50% at a concentration (IC50) of 6.2 x 10(-10) M and by 98% at 1 x 10(-7) M. SWA11-ricin A chain had an IC50 of 4.4 x 10(-10) M against the NCI-H69 classic SCLC cell line but showed no cytotoxic activity against the human lung adenocarcinoma cell line NCI-H23 at a concentration of 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 / Q000008:administration & dosage*; D000951:Antigens, Neoplasm / Q000276:immunology*; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology*; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D012276:Ricin / Q000008:administration & dosage*
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000922:Immunotoxins; D012276:Ricin