TUMOR-THERAPY WITH RADIOLABELED ANTIBODIES - OPTIMIZATION OF THERAPY

The promise of radiolabelled immunoglobulin therapy (RIT) for selectiv e, 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 radiolab elled antibodies does not provide sufficient tumour targeting. However , intracompartmental administration may solve this problem, particular ly if tumour reactive IgM is used. Clinical progress in RIT depends on understanding the important RIT variables: antigen, antibody, radiois otope, conjugation chemistry, activity escalation, fractionation and p rotein dose. These are reviewed and a new translational decision tree/ flow diagram is presented that can limit analysis to the most importan t RIT variables for a particular disease. These variables may differ d epending on the type and stage of cancer, but the guiding principles i n RIT development remain the same: selectivity and accountability. The proper application of these principles leads to the definition of a n ew series of phase I, ii, III studies. These studies are more appropri ate for the clinical exploration of RIT and place an emphasis on thera peutic ratio rather than toxicity.