CLINICAL SCREENING OF MONOCLONAL-ANTIBODIES 323 A3, CSF-25 AND K928 FOR SUITABILITY OF TARGETING TUMORS IN THE UPPER AERODIGESTIVE AND RESPIRATORY-TRACT/

Immunohistochemical characterization of three monoclonal antibodies (M Abs), designated 323/A3, SF-25 and K998, on a panel of 330 head and ne ck and lung tumours indicated their potential for targetting tumours i n the upper aerodigestive and respiratory tract. Subsequently, MAbs we re screened in a clinical phase I/II radioimmunoscintigraphic (RIS) tr ial for the detection of primary tumours and lymphnode metastases in p atients with histologically proven squamous cell carcinoma of the head and neck (HNSCC). In 10 HNSCC patients MAbs 323/A3 F(ab')2 (n = 3), c himeric (mouse-human) SF-25 IgG (n = 1), and K928 IgG (n=6) were evalu ated for their suitability for tumour targetting. Monoclonal antibodie s 323/A3 and K928 were shown to be capable of detection of HNSCC. Howe ver, there was uptake at non-tumour sites, for MAb 323/A3 in the thyro id gland, liver and skeleton, probably bone marrow, and for MAb K928 i n liver, spleen and the skeleton, probably bone marrow. At a higher K9 28 dose, uptake in the liver was diminished but still substantial. cSF -25 was not capable of detecting HNSCC, due to the rapid and extensive uptake at non-tumour sites such as liver, spleen, brain and the skele ton, probably bone marrow. Radioactivity uptake at non-tumour sites co uld be mainly explained by the presence of good accessible antigenic s ites and will definitely limit the application of these pan-carcinoma MAbs for therapeutic purposes.