Potential for targeting head and neck squamous cell carcinoma with monoclonal antibody K984.
In previous reports we have described the development of mAb K984, reactive with an epitope expressed on the outer cell surface of undifferentiated, proliferating cells in normal stratified squamous epithelia and their neoplastic counterparts. The K984 antigen was also found to be homogeneously expressed by in vitro cultured squamous cell carcinoma (SCC) cell lines. In the present study we demonstrate that mAb K984 induces a significant, dose-dependent growth inhibition when SCC cells are grown in vitro as monolayer cultures in the presence of mAb K984. These data seem to indicate that mAb K984 has potential for tumour targeting, especially in a therapeutic setting. As a first approach to evaluate the suitability of mAb K984 for tumour targeting in vivo, radiolabelled mAb K984 was administered to SCC-xenografted nude mice. Selective tumour accumulation of mAb K984 was observed. Tumour to blood ratios and tumour to non-tumour ratios, as based on the biodistribution data, were at least ten times higher in case of the specific mAb K984 when compared to another non-specific, isotype-matched control antibody. mAb K984 was also capable of visualizing tumour deposits in xenografted nude mice. The corollary of these findings is that the mAb K984-defined antigen probably is involved in the regulation of proliferation of stratified squamous epithelium and squamous cell carcinoma and that mAb K984 has potential for specific tumour targeting.
Department of Otolaryngology, Free University Hospital, Amsterdam, The Netherlands.
A H
AH
Schrijvers
M
M
Gerretsen
M
M
van Walsum
B J
BJ
Braakhuis
J J
JJ
Quak
G B
GB
Snow
G A
GA
van Dongen
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000276:immunology* / Q000473:pathology; D002455:Cell Division; D000939:Epitopes; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology* / Q000473:pathology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011877:Radionuclide Imaging; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D000939:Epitopes