Clinical screening of monoclonal antibodies 323/A3, cSF-25 and K928 for suitability of targetting tumours in the upper aerodigestive and respiratory tract

Immunohistochemical characterization of three monoclonal antibodies (MAbs), designated 323/A3, SF- 25 and K928, on a panel of 330 head and neck and lung tumours indicated their potential for targetting tumours in the upper aerodigestive and respiratory tract. Subsequently, MAbs were screened in a clinical phase I/II radioimmunoscintigraphic (RIS) trial for the detection of primary tumours and lymph- node metastases in patients with histologically proven squamous cell carcinoma of the head and neck (HNSCC). In 10 HNSCC patients MAbs 323/A3 F(ab')2 (n=3), chimeric (mouse-human) SF-25 IgG (n=l), and K928 IgG (n=6) were evaluated for their suitability for tumour targetting. Monoclonal antibodies 323/A3 and K928 were shown to be capable of detection of HNSCC. However, there was uptake at non-tumour sites, for MAb 323/A3 in the thyroid gland, liver and skeleton, probably bone marrow, and for MAb K928 in liver, spleen and the skeleton, probably bone marrow. At a higher K928 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 skeleton, probably bone marrow. Radioactivity uptake at non-tumour sites could be mainly explained by the presence of good accessible antigenic sites and will definitely limit the application of these pan-carcinoma MAbs for therapeutic purposes.