THE FEASIBILITY OF RADIOIMMUNOTHERAPY OF HEAD AND NECK-CANCER

Since the introduction of the hybridoma technology by Kohler and Milst ein (Nature 1975, 256, 495-497), tremendous effort has been put in the realisation of Ehrlich's concept of the magic bullet, which was propo sed as early as the beginning of the century. The first clinical studi es for radioimmunoscintigraphy (RIS) and radioimmunotherapy (RIT) with radiolabelled antibodies were undertaken in the early 1980s. Since th en, RIS has been performed on thousands of patients with various types of malignancies, like colon carcinoma, lung carcinoma, breast carcino ma, neuroblastoma, T-cell lymphoma and ovarian carcinoma. In addition, a substantial number of therapy trials with radiolabelled antibodies have been performed. The developments for head and neck squamous cell carcinoma (HNSCC) have only recently been able to catch up with these events to some extent. One of the main reasons for this slow progress has been the lack of monoclonal antibodies (Mab) with specificity for HNSCC. Although there are as yet no real tumour specific antigens know n for HNSCC, which also holds true for the majority of malignancies ar ising from other tissues, we now have the availability of a number of Mab with high specificity for HNSCC and with a very restricted reactio n pattern with normal tissues. Labelled with I-131, these Mab have bee n shown to be highly capable to localise in HNSCC xenografts in nude m ice. Based on these promising data, patient studies with one of these Mab, designated Mab E48, labelled with Tc-99m, were started to evaluat e the feasibility of RIS in patients with head and neck cancer. The fi rst results of these studies indicated the capacity of Tc-99m-labelled Mab E48 F(ab')(2) as well as IgG to detect metastatic and recurrent d isease in these patients. These data justified further studies investi gating the possibilities for RIT with this Mab. In preclinical experim ents, the capacity of (131m)-labelled Mab E48 IgG to eradicate establi shed HNSCC tumours in nude mice was shown. Following the latest develo pments in the field of radioimmunoconjugate chemistry and anticipating the need for more appropriate radionuclides for clinical applications , a technical protocol for the labelling of Mab with Re-186 was develo ped. Labelled with Re-186, Mab E48 appears to be even better suited to eradicate established tumours than when labelled with I-131. Based on these encouraging observations we are now making preparations for the first RIT studies with Re-186-labelled Mab E48 in patients with head and neck cancer.