IMMUNOLOGICAL RESPONSE TO INTRATHECAL AND SYSTEMIC TREATMENT WITH GANGLIOSIDE ANTIBODY R-24 IN PATIENTS WITH MALIGNANT-MELANOMA

Murine monoclonal antibody (MAb) R-24 reacts with the ganglioside GD3 that is highly expressed on malignant melanoma. 2 patients with melanosis of the meninges received MAb R-24 intrathecally. Regressive changes in tumour cells were observed in both patients after intrathecal application of MAb R-24 (1-10 mg, 8-10 h, over 5-6 weeks). The first patient suffered from brain metastases and died a few weeks later, whereas the second achieved a complete remission with no evidence of disease 6 years after intrathecal R-24 treatment. No R-24-related neurotoxicity has occurred to date. The administration of MAb R-24 caused an increase of inflammatory cells in the cerebrospinal fluid (CSF) of both patients. Cytotoxic lymphocytes, cultured from the CSF, showed high cytolytic activity against allogeneic melanoma cells in vitro. In addition, 15 patients with advanced melanoma, in which the brain was not affected, were treated with R-24 intravenously using high dose R-24 (5 or 10 mg/m(2)) or low dose R-24 (1 mg/m(2)). No remissions were registered in the high dose group, with only 1/6 patients experiencing a mixed response. In contrast, 2/9 patients treated with low dose R-24 achieved a partial remission, one achieving a minor response and the other a mixed response. Toxicity was related to the dose of R-24 administered. Urticaria, burning and pruritus were the prominent side-effects, mostly occurring at the high dose level. Immunological monitoring during and after intravenous treatment showed no significant changes in peripheral blood lymphocytes, natural killer cell activity or antibody-dependent cellular cytotoxicity, although transient changes were observed. There was no correlation between immunological parameters and clinical response.