Irradiation of singly and doubly transduced murine neuroblastoma cells expressing B7-1 and producing interferon-gamma reduces their capacity to induce systemic immunity

We have previously reported that immunization with low major histocompatibility complex (MHC) class I expressing murine neuroblastoma (neuro-2a) transduced with B7-1 fails to induce significant protection to wild-type tumor challenge. In this study we investigated whether B7-1 expressing neuro-2a cells can stimulate an effective T-cell response if they were cotransduced with the interferon-gamma (IFN-γ) gene to upregulate MHC class I. Transfer of both the IFN-γ and B7-1 genes into neuro-2a (N-2a/B7-1/IFN) almost completely abrogated the tumorigenic potential of this tumor and improved survival when compared with mice receiving the single transductants, N-2a/IFN and N-2a/B7-1. Rejection of N-2a/B7-1/IFN was mediated primarily by CD8⁺ T cells. When irradiated tumor cells were tested, IFN-γ gene transfer into neuro-2a significantly increased immunogenicity, but transfer of the B7-1 gene did not. However, nonirradiated N-2a/B7-1, N-2a/IFN, and N-2a/B7-1/IFN cells were significantly more effective in eliciting systemic immunity against subsequent wild-type tumor challenge than their irradiated counterparts. N-2a/B7-1/IFN was more immunogenic than N-2a/B7-l but not more than N-2a/IFN, indicating that B7-1 does not further increase immunogenicity of neuro-2a over that induced by IFN-γ transduction. These findings should be considered when designing gene modified tumor vaccines for use in human trials.