Tumour therapy with radiolabelled antibodies: optimisation of therapy

The promise of radiolabelled immunoglobulin therapy (RIT) for selective, patient friendly, cancer treatment has not yet been fulfilled. Only patients with haematological malignancies show sizable response rates after RIT. With solid tumours, intravenous administration of radiolabelled antibodies does not provide sufficient tumour targeting. However, intracompartmental administration may solve this problem, particularly if tumour reactive IgM is used. Clinical progress in RIT depends on understanding the important RIT variables: antigen, antibody, radioisotope, conjugation chemistry, activity escalation, fractionation and protein dose. These are reviewed and a new translational decision tree/flow diagram is presented that can limit analysis to the most important RIT variables for a particular disease. These variables may differ depending on the type and stage of cancer, but the guiding principles in RIT development remain the same: selectivity and accountability. The proper application of these principles leads to the definition of a new series of phase I, II, III studies. These studies are more appropriate for the clinical exploration of RIT and place an emphasis on therapeutic ratio rather than toxicity.