Anti-tumour activity against B16-F10 melanoma with a GM-CSF secreting allogeneic tumour cell vaccine

Genetic modification of tumour cells with the GM-CSF encoding gene renders these cells more potent, as autologous tumour cell vaccine, than their wild -type counterparts. However, autologous Vaccines are impractical for wide-s cale clinical use and we have therefore investigated the efficacy of the GM -CSF genetic modification approach with an allogeneic whole cell tumour vac cine. In this report, we show that the allogeneic K1735-M2 (H-2k) melanoma cell vaccine induces a specific protective anti-tumour response against the syngeneic B16-F10 (H-2b) melanoma tumour in C57BL/6J mice. In vitro T cell work demonstrated that vaccination of animals with the allogeneic cell vac cine generated cytotoxic T cells specific for the autologous tumour. In viv o T cell subset depletion experiments also illustrated that this anti-tumou r effect was mediated by both CD4+ve and CD8+ve T cells, suggesting that th e allogeneic vaccine may operate through the 'cross-priming' phenomenon whe reby tumour antigens are processed and presented to T cells by the host's o wn antigen presenting cells (APC). Thus, we transduced K1735-M2 cells with a GM-CSF expressing retroviral vector and showed antitumour activity of the GM-CSF secreting K1735-M2 cells as a therapeutic vaccine against the synge neic B16-F10 tumour. Our data imply that GM-CSF genetically modified alloge neic whole cell tumour vaccines could be successful in the clinic. in addit ion, more potent combination gene therapy strategies could be tested using this therapeutic allogeneic vaccine model.