The development of non-responsiveness to immunotherapy with monoclonal anti-idiotypic antibodies in a patient with B-CLL
A patient having a B cell chronic lymphocytic leukaemia was treated with a monoclonal anti-idiotypic antibody (MoAb anti-id). Up to 24.5 g of MoAb anti-id has been administered to the patient over a period of 1 year without serious side effects. Despite a substantial amount of serum idiotype (id = 100 micrograms/ml) and a low expression of id on the tumour cells (+/- 6000 molecules per cell) clearance of serum id and a marked tumour reduction was obtained. Therapy resistance developed and coincided with a decreased clearance rate of circulating id-anti-id immune complexes and an increased modulation of cellular id expression, in vivo. This suggests that a decreased clearance rate of anti-id coated tumour cells provided more time for id modulation in vivo, resulting in therapy resistance. Therefore, the overall capacity of the natural effector system may have an important influence on the ultimate therapeutic effect of immunotherapy with MoAb anti-id. Although the partial remission obtained was not long-lasting, this study shows that MoAb anti-id therapy can be effective even when id expression on the tumour cells is low and a substantial amount of serum id is present.
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