The Application of Monoclonal Antibodies in the Treatment of Lymphoma
Monoclonal antibodies (mAbs) appear to offer many benefits for the treatment of cancer and in particular lymphoma (1 ). They are natural products that can be made with precise specificity and in almost unlimited amounts. In addition, mAbs can be selected
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7 The Application of Monoclonal Antibodies in the Treatment of Lymphoma Martin J. Glennie, Jamie Honeychurch, Ruth R. French, and Alison L. Tutt 1. Introduction Monoclonal antibodies (mAbs) appear to offer many benefits for the treatment of cancer and in particular lymphoma (1). They are natural products that can be made with precise specificity and in almost unlimited amounts. In addition, mAbs can be selected or engineered to efficiently recruit the body’s effector systems, such as complement and natural killer cells, against the unwanted cells in much the same way as they might destroy an invading pathogen. Unfortunately, progress in the clinic has been slow, and the cytotoxic activity achieved with mAb in vitro has failed to be transferred into patients. Despite this rather disappointing outcome, recent results in treating non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL) with anti-CD20 and anti-CD52 (CAMPATH 1) mAb suggest, at least for certain neoplasms, that the situation may be changing (2,3). Stevenson and colleagues (personal communication) have recently achieved more than 70% complete responses in posttransplant lymphoma treated with a chimeric anti-CD20 mAb, and Maloney and co-workers (2) recently reported a 50% response rate in relapsed, low-grade, NHL, with a 10–11 mo duration. Encouragingly, patients in these studies did not raise antibody responses to the treatment anti-CD20 mAb and, unlike the situation following therapy in many lymphomas with anti-idiotype (Id) mAb, the emergence of antigen-negative tumors has not been seen (4). To underline its clinical success, anti-CD20 mAb (Rituximab) has now become the first anticancer mAb to become licensed by the FDA for lymphoma treatment. One of the most encouraging aspects of Rituximab treatment is that, in addition to its therapeutic activity, which appears to match that of more conFrom: Methods in Molecular Medicine, Vol. 40: Diagnostic and Therapeutic Antibodies Edited by: A. J. T. George and C. E. Urch © Humana Press Inc., Totowa, NJ
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ventional chemotherapy in a similar setting, it has very few adverse effects and can be given to patients who are in poor condition with advanced disease. Early experience suggests that it will be this lack of adverse effects that will be its most attractive feature. Perhaps the most disappointing aspect of the work to date with anti-CD20 mAb has been the low frequency of complete remissions (CR) (approx 8%). Failure to eradicate all tumor shows that the treatment conditions have yet to be optimized or, as has been pointed out by many workers, mAbs are not ideal reagents for dealing with bulky disease and may be more appropriate in the setting of minimal disease. In this regard it will be interesting to see how this reagent performs as “first-line” therapy in NHL before the patient’s immune system has become damaged by disease and therapy. Encouraging results are already appearing from a study in which anti-CD20 mAb is being used in combination with chemotherapy. Although t
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