Antitumor activity of murine monoclonal antibody NCC-ST-421 on human cancer cells by inducing apoptosis.
BACKGROUND
The murine monoclonal antibody NCC-ST-421 (ST-421) recognizes dimeric Le(a) antigen expressed on gastrointestinal cancer cells.


METHODS
Direct antitumour activity of ST-421 was evaluated using dimeric Le(a) positive cell lines Colo 205, Colo 201, HT-29 and WiDr; and negative cell lines MX-1 and K562.


RESULTS
While time- and concentration-dependent antitumour activity was observed against Colo 205 and Colo 201, no antitumour activity was detected against the other cell lines tested in an in vitro cytotoxicity assay. When ST-421 was administered intraperitoneally daily for 2 weeks to severe combined immunodeficient (SCID) mice transplanted with tumour xenografts, inhibition of tumour growth was observed against Colo 205, and to a lesser extent HT-29 and WiDr. Anti-asialo GM1 antibody did not block this antitumour activity, suggesting ST-421 has a direct cytotoxic effect. The degree of antitumour activity of ST-421 dependent on the grade of Le(a)-expression as detected by immunohistochemical staining.


CONCLUSIONS
Flow cytometric and immunohistochemical analysis suggests the induction of apoptosis may play a key role in the direct antitumour activity of ST-421 on Colo 205 cells.
Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
H
H
Ishizuka
M
M
Watanabe
T
T
Kubota
S W
SW
Matsuzaki
Y
Y
Otani
M
M
Kitajima
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use* / Q000633:toxicity; D000951:Antigens, Neoplasm / Q000627:therapeutic use* / Q000633:toxicity; D000970:Antineoplastic Agents / Q000627:therapeutic use* / Q000633:toxicity; D017209:Apoptosis; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology / Q000628:therapy*; D005260:Female; D005434:Flow Cytometry; D005732:Gangliosides / Q000276:immunology; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute; D008297:Male; D051379:Mice; D016513:Mice, SCID; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D005732:Gangliosides; C113916:NCC-ST-421 antigen; C082657:dimeric Le(a) antigen, human