2 '-2 '-Difluorodeoxycytidine: In vitro effects on cell-mediated immune response

Little or no data are available on the immunotoxicity of the new deoxycytid ine analogue, gemcitabine (2'-2'-Difluorodeoxycytidine, dFdC). The drug was tested on natural killer (NK), interleukin 2-activated killer (LAK) and an tigen-dependent cytotoxic effector cells (CTL) activity. NK cells were trea ted for 16 hours and then tested against K562 cell line. LAK cells were pre treated for 16 hours before or after IL2 stimulation, and tested against DA UDI cells on day 4. CTL were pretreated for 16 hours on day -1 or on day 4 of coculture, and then tested against MT-2 on day 5. Cytotoxic activity was evaluated by a 4 Cr-51-release assay. The results indicate that dFdC inhib its hours markedly LAK or CTL generation, but does so less efficiently on " mature" LAK or CTL lymphocyte function and only slightly on NK cell activit y. Therefore dFdC cart be considered immunotoxic for either natural or anti gen-dependent cell-mediated immunity.