Tumour-growth suppression in nude mice by a murine monoclonal antibody: factors hampering successful therapy.
The murine MAb C215 has been shown to mediate ADMMC in vitro and to have a tumour-growth-suppressive effect on xenografted COLO 205 human colocarcinoma cells in nude mice. To overcome the limitations of MAb therapy, it is necessary to understand the underlying mechanisms of tumour-growth suppression. In the present work, we have used C215 to define the importance of different parameters involved in tumour therapy with murine IgG2a antibodies. The results show that there exists a period of roughly 2 days after inoculation into animals during which the tumour cells are sensitive to an inhibitory antibody-mediated effect. After this initial period, the in-vivo sensitivity of tumour cells to antibody-mediated inhibition is much reduced. Tumour cells can remain "dormant" and, despite ongoing antibody treatment, develop into tumours with a reduced growth rate, which is not caused by outgrowth of antigen-deficient tumour cells. Finally, a pronounced dependence of antibody-mediated tumour suppression on antibody dose was observed.
Johansson
C
C
Pharmacia CanAg, Göteborg, Sweden.
Segrén
S
S
Lindholm
L
L
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000939:Epitopes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000939:Epitopes