Efficacy of cytokine gene transfection may differ for autologous and allogeneic tumour cell vaccines

Whole tumour cells are a logical basis for generating immunity against the cancers they comprise or represent. A number of human trials have been init iated using cytokine-transfected whole tumour cells of autologous (patient- derived) or allogeneic [major histocompatibility complex (MHC)disparate] or igin as vaccines. Although precedent exists for the efficacy of autologous- transfected cell vaccines in animal models, little preclinical evidence con firms that these findings will extrapolate to allogeneic-transfected cell v accines. In order to address this issue a murine melanoma cell line (K1735) was transfected to secrete interleukin (IL)-2, IL-4. IL-7 or granulocyte-m acrophage colony-stimulating factor (GM-CSF); cytokines currently in use in trials. The efficacy of these cells as irradiated vaccines was tested head -to-head in syngeneic (C3H) mice and in MHC-disparate (C57BL/6) mice, the f ormer bring subsequently challenged with K1735 cells and the latter with na turally cross-reactive B16-F10 melanoma cells. Whilst the GM-CSF-secreting vaccine was the most effective at generating protection in C3H mice, little enhancement in protection above the wild-type vaccine was seen with any of the transfections for the allogeneic vaccines, even though the wild-type v accine was more effective than the autologous B16-F10 vaccine. Anti-tumour cytotoxic T-lymphocyte (CTL) activity was detected in both models but did n ot correlate well with protection, whilst in, vitro anti-tumour interferon- gamma (IFN-gamma) secretion tended to be higher following the GMCSF-secreti ng vaccine. Cytokine transfection of vaccines generally increased anti-tumo ur CTL activity and IFN-gamma secretion (T helper type 1 response). Further studies in other model systems are required to confirm this apparent lack of benefit of cytokine transduction over wild-type allogeneic vaccines, and to determine which in vitro assays will correlate best with protection in vivo.