Monoclonal Antibodies For Treatment Of Classical Hodgkins Lymphoma

Among the different target antigens on Reed-Sternberg cells, CD30 seems to be the most promising, since it is expressed at very high levels.75 So far, two anti-CD30 MoAbs have been developed, the humanized SGN-3076 and the fully human MDX-60.77The SGN-30 chimeric anti-CD30 antibody has demonstrated antitumor activity in preclinical models of Hodgkin's lymphoma and anaplastic large cell lymphoma. In a phase I single-dose trial, SGN-30 MoAb showed minimal toxicity with doses from 1 to 15 mg/kg, and antitumor activity was documented in 15% of patients (2 of 13). In a phase I/II dose-escalation study of 6 weekly infusions of SGN-30 at doses of 2, 4, 8, and 12 mg/kg, the MOAb was very well tolerated up to 8 mg/kg, and it was associated with a moderate activity.78

MDX-060 is a fully human IgG MoAb that recognizes CD30 and mediates killing of Reed-Sternberg cells in vitro and in xenograft tumor models. In a phase I/II dose-escalation study in patients with relapsed or refractory Hodgkin's lymphoma and other CD30+ lymphomas, MDX-060 was administered intravenously at dose levels of 0.1, 1, 5, 10, or 15 mg/kg, weekly for 4 weeks, with no dose-limiting toxicity. While the efficacy assessment has not been completed yet in all patients, preliminary results indicate that MDX-060 is well tolerated and has a clinical activity.79 Currently, humanized as well as fully human anti-CD30 MoAbs are being tested in clinical phase I/II studies. These MoAbs could engage the human immune system against Hodgkin's lymphoma and are capable of inducing apoptosis of Hodgkin's and Reed-Sternberg cells. In addition, these MoAbs could be combined with conventional chemotherapy and further improve the therapy of Hodgkin's lymphoma.

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