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 far the treatmen t of patients with minimal residual disease of head-and-neck squamous- cell carcinoma (HNSCC). For this purpose we developed MAb U36, recogni zing a 200-kDa antigen expressed on the outer cell surface of squamous -cell carcinomas and their normal counterparts. Clinical radioimmunosc intigraphy (RIS) and biodistribution studies have shown that the MAb-U 36-defined antigen is a suitable target molecule for antibody-based th erapy of head-and-neck cancer. In the present study we further charact erized the antigen by cDNA cloning. The cDNA was isolated by expressio n cloning in COS-7 cells. Sequence analysis and database searching rev ealed that the MAb-U3C-defined antigen is identical to the squamous-ce ll-specific CD44 splice variant epican. The epitope recognized by MAb U36 was mapped by screening overlapping synthetic peptides of the epic an-specific region encoded by exon 7-11 (v3-v7), and appeared to be lo cated in the v6 domain. The applicability of MAb U36 for targeting hum an tumors of various origin expressing the CD44vb domain is discussed. (C) 1996 Wiley-Liss, Inc.