The feasibility of radioimmunotherapy of head and neck cancer

Since the introduction of the hybridoma technology by Kohler and Milstein ( Nature 1975, 256, 495–497), tremendous effort has been put in the realisation of Ehrlich's concept of the magic bullet, which was proposed as early as the beginning of the century. The first clinical studies for radioimmunoscintigraphy (RIS) and radioimmunotherapy (RIT) with radiolabelled antibodies were undertaken in the early 1980s. Since then, RIS has been performed on thousands of patients with various types of malignancies, like colon carcinoma, lung carcinoma, breast carcinoma, 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 known for HNSCC, which also holds true for the majority of malignancies arising from other tissues, we now have the availability of a number of Mab with high specificity for HNSCC and with a very restricted reaction pattern with normal tissues. Labelled with 131 I, these Mab have been shown to be highly capable to localise in HNSCC xenografts in nude mice. Based on these promising data, patient studies with one of these Mab, sesignated Mab E48, labelled with 99m Tc, were started to evaluate the feasibility of RIS in patients with head and neck cancer. The first results of these studies indicated the capacity of 99m Tc-labelled Mab E48 F(ab′) 2, as well as IgG to detect metastatic and recurrent disease in these patients. These data justified further studies investigating the possibilities for RIT with this Mab. In preclinical experiments, the capacity of 131 I-labelled Mab E48 IgG to eradicate established HNSCC tumours in nude mice was shown. Following the latest developments 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 186 Re was developed. Labelled with 186 Re, Mab E48 appears to be even better suited to eradicate established tumours than when labelled with 131 I. Based on these encouraging observations we are now making preparations for the first RIT studies with 186 Re-labelled Mab E48 in