Expression and characterization of two differentiation antigens in human stratified squamous epithelia and carcinomas

Abstract

Using viable cells of a human squamous-cell carcinoma (SCC) cell line as immunogen, we generated 2 monoclonal antibodies, MAbs K984 and K928, to SCC surface antigens. Immunoperoxidase staining of frozen sections of normal epidermis revealed that MAb K984 reacts with the poorly differentiated basal cells, while MAb K928 is reactive with the more highly differentiated suprabasal cells. A similar complementary reaction pattern of these antibodies was demonstrated in the majority of well-differentiated human tumors and some moderately differentiated SCCs. In contrast, simultaneous reactivity of MAb K984 and K928 was found for the majority of cells within other well- and moderately differentiated SCCs, as well as all poorly differentiated SCCs. Further biochemical characterization indicated that the antigen recognized by MAb K984 is similar to the one recognized by MAb SF-25. MAb K928 recognizes a 50- to 55-kDa molecule under non-reducing conditions. Antibodies with similar features to MAb K928 have not been described previously. The antigens recognized by MAbs K984 and K928 can be regarded as novel markers associated with cellular maturation in squamous epithelia. The antigen detected by MAb K984 is probably associated with the proliferating fraction in SCCs.

Radioimmunotherapy of human head and neck squamous cell carcinoma xenografts with 131I-labelled monoclonal antibody E48 IgG

“…The presence of the MAb E48 defined antigen in normal tissues in the clinical situation will obviously influence the pharmacokinetics and biodistribution of radiolabelled MAb E48. In clinical radioimmunoscintigraphy studies using 9'Tc-labelled MAb E48 (Fab')2 fragment we observed uptake of radioactivity in normal oral mucosa and adrenal glands (van Dongen et al, 1992). Uptake in these tissues seems to be diminished when using whole IgG.…”

“…Thusfar however, no HNSCC-specific MAbs have been available to test the efficacy of RIT to eradicate HNSCC xenografts in an experimental setting. Therefore, we have developed a panel of MAbs, among which MAb E48, raised against HNSCC (Quak et al, 1990a;Quak et al, 1990b;Quak et al, 1992). MAb E48 recognises a 20-22kD antigen, on normal tissues selectively expressed on stratified squamous epithelia and transitional epithelium of the bladder.…”

“…Biodistribution and imaging studies with tracer amounts of '3'I-labelled E48 IgG and F(ab')2 fragments already demonstrated the capacity of MAb E48 for specific delivery of radioisotope to HNSCC xenografts (Quak et al, 1989;Gerretsen et al, 1991). Recent data from an ongoing phase I/II trial with intraveneously administered 99'Tclabelled MAb E48 F(ab')2 and IgG in patients with HNSCC indicate that MAb E48 is highly capable of detecting metastatic and recurrent disease (van Dongen et al, 1992). In the present study we demonstrate a dose dependent growth delay, regression and complete remission of established tumours by injection of single doses "1'1-labelled MAb E48 in nude mice bearing HNSCC xenografts.…”

Potential for targeting head and neck squamous cell carcinoma with monoclonal antibody K984

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Summary.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 [28,30]. The K984 antigen was also found to be homogeneously expressed by in vitro cultured squamous cell carcinoma (SCC) cell lines.

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Die zukünftige Bedeutung monoklonaler Antikörper bei der adjuvanten Therapie von Kopf-Hals-Karzinomen

“…Mabs, gekoppelt an Radionukleide, haben den Vorteil einer auf den Tumor allein ausge richteten Bestrahlung [4], Aufgrund der hohen Ansprech rate ist für die Behandlung von Plattenepithelkarzinomen des Kopf-und Halsgebietes eine Radioimmuntherapie (RIT) besonders geeignet [5], Bei anderen therapeuti schen Versuchen werden unkonjugierte Mabs wegen ihrer zytotoxischen Eigenschaften benutzt, beispielsweise zur Vermittlung von immunologischen Wirkmechanismen (antikörperabhängige Zytotoxizität) [6], Bisher konnte das grosse Potential der Mabs nicht genutzt werden, da spezifische Mabs für Kopf-Hals-Plattenepithelkarzinome nicht verfügbar waren. Seit kurzem sind wir jedoch in der Lage, Mabs gegen Oberflächenanti gene von Plattencpithelkarzinomen zu produzieren [7][8][9][10]. In dieser Arbeit werden die mit solchen Mabs in vor klinischen und klinischen Studien erreichten Ergebnisse mitgeteilt.…”