title: MAb U36, a novel monoclonal antibody successful in immunotargeting of squamous cell carcinoma of the head and neck.
abstract: Using viable cells of a human head and neck squamous cell carcinoma (HNSCC) cell line as immunogen, we developed monoclonal antibody (MAb) U36. Immunohistochemical examination revealed distinct surface labeling of MAb U36 with normal human squamous epithelium and squamous cell carcinomas of distinct sites of origin; head and neck, lung, esophagus, cervix, and epidermis. MAb U36 shows high affinity binding (affinity constant, 3.5 x 10(10)/M) with a cell surface antigen expressed by in vitro cultured HNSCC cell lines. Similarity of the reactivity profiles of MAb U36 and MAb E48, currently the most promising antibody described for specific targeting of HNSCC in patients, warranted further comparison of these MAbs. MAb U36 recognizes a M(r) 200,000 antigen, which is different from the MAb E48 defined antigen. Furthermore, comparison of immunohistochemical staining patterns of MAb U36 and MAb E48 on a broad panel of primary HNSCC sections revealed more extensive staining for MAb U36: more tumors showed reactivity with MAb U36 and more tumor cells per tumor showed positive reaction, and staining was found to be more intense. MAb U36 does not show cross-reactivity with mouse, rat, pig, sheep, or bovine tongue epithelium. As a first approach to evaluate the suitability of MAb U36 for tumor targeting in vivo, radiolabeled MAb U36 was administered to athymic nude mice bearing human HNSCC xenografts on both flanks. Selective tumor accumulation of the radioimmunoconjugate was observed. Mean tumor uptake (in percent injected dose/g wet-weight of tissue) of MAb U36 at days 1, 2, 3, 5, 7, and 12 was 15.1, 17.9, 24.0, 21.0, 25.8, and 16.0%, respectively. The tumor to blood ratio at day 1 was 0.9 and increased up to 3.8 at day 12. The tumor uptake at day 12 was at least 10 times higher when compared to other tissues. The corollary of these findings is that MAb U36 harbors high potential for specific targeting of HNSCC.
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: A H
authors.initials: AH
authors.lastname: Schrijvers
authors.forename: J J
authors.initials: JJ
authors.lastname: Quak
authors.forename: A M
authors.initials: AM
authors.lastname: Uyterlinde
authors.forename: M
authors.initials: M
authors.lastname: van Walsum
authors.forename: C J
authors.initials: CJ
authors.lastname: Meijer
authors.forename: G B
authors.initials: GB
authors.lastname: Snow
authors.forename: G A
authors.initials: GA
authors.lastname: van Dongen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000951:Antigens, Neoplasm / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000276:immunology; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D016719:Radioimmunodetection
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D007457:Iodine Radioisotopes