Chemical xenogenization of cancer cells: In vitro studies with human melanomas

Previous studies performed in our laboratory showed that in vivo or in vitro treatment of murine lymphomas with triazene compounds (TZC) induces the appearance of novel tumor-associated antigens (i.e. 'chemical xenogenization', CX), or of membrane structures susceptible to natural immunity (NI), i.e. NI-related CX (CX/NI). The present investigation was performed to explore whether CX/NI could be induced in cultured human melanoma cells by treatment with monomethyl-triazene-benzoic acid potassium salt (MTBA), an in vitro active TZC. The results show that 2 over 3 MTBA-treated lines became more susceptible than the original melanoma to natural cytotoxic effector cells (i.e. NK or LAK cells). TZC-treated melanomas did not show substantial changes with respect to untreated tumors in the expression of HLA class I or class II antigens and of two epitopes of a high-molecular weight melanoma-associated antigen. In addition parental and MTBA-treated lines were scarcely susceptible to killing by 66 h continuous exposure to MTBA, whereas all lines were sensitive to Cisplatin and with the exception of one MTBA-treated line to Ara-C. Therefore no relationship was found between chemosensitivity to MTBA and susceptibility to a presumable induction of CX/NI by the same agent. The present study suggests the hypothesis that in vivo CX/NI could play a potential role in TZC-based chemoimmunotherapy of melanoma patients.