Monoclonal antibody U36, a suitable candidate for clinical immunotherapy of squamous-cell carcinoma, recognizes a CD44 isoform.
At present, tumor-targeting with monoclonal antibodies (MAbs) is among the most promising novel adjuvant-therapy modalities for the treatment of patients with minimal residual disease of head-and-neck squamous-cell carcinoma (HNSCC). For this purpose we developed MAb U36, recognizing a 200-kDa antigen expressed on the outer cell surface of squamous-cell carcinomas and their normal counterparts. Clinical radioimmunoscintigraphy (RIS) and biodistribution studies have shown that the MAb-U36-defined antigen is a suitable target molecule for antibody-based therapy of head-and-neck cancer. In the present study we further characterized the antigen by cDNA cloning. The cDNA was isolated by expression cloning in COS-7 cells. Sequence analysis and database searching revealed that the MAb-U36-defined antigen is identical to the squamous-cell-specific CD44 splice variant epican. The epitope recognized by MAb U36 was mapped by screening overlapping synthetic peptides of the epican-specific region encoded by exon 7-11 (v3-v7), and appeared to be located in the v6 domain. The applicability of MAb U36 for targeting human tumors of various origin expressing the CD44v6 domain is discussed.
Van Hal
N L
NL
Department of Otolaryngology/Head and Neck Surgery, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
Van Dongen
G A
GA
Rood-Knippels
E M
EM
Van Der Valk
P
P
Snow
G B
GB
Brakenhoff
R H
RH
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D003001:Cloning, Molecular; D018604:Epitope Mapping; D006258:Head and Neck Neoplasms / Q000628:therapy*; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology*; D008969:Molecular Sequence Data
D000911:Antibodies, Monoclonal; D018960:Hyaluronan Receptors