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

Abstract

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-gamma) gene to upregulate MHC class I. Transfer of both the IFN-gamma 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-gamma 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/B7-1 but not more than N-2a/IFN, indicating that B7-1 does not further increase immunogenicity of neuro-2a over that induced by IFN-gamma transduction. These findings should be considered when designing gene modified tumor vaccines for use in human trials.

• Authors: E Katsanis, M A Bausero, A Panoskaltsis-Mortari, B B Dancisak, Z Xu, P J Orchard, C G Davis, B R Blazar
• Journal: Cancer gene therapy (Cancer Gene Ther) 1996 Mar-Apr Vol. 3 Issue 2 Pg. 75-82 ISSN: 0929-1903 [Print] England
• PMID: 8729905 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• B7-1 Antigen
• Interferon-gamma

Topics

• Animals
• B7-1 Antigen (biosynthesis, radiation effects)
• CD4-CD8 Ratio
• Dose-Response Relationship, Radiation
• Female
• Immunity, Cellular (radiation effects)
• Interferon-gamma (biosynthesis, metabolism)
• Major Histocompatibility Complex (immunology)
• Mice
• Neoplasms, Experimental (drug therapy)
• Neuroblastoma (immunology)
• Survival Rate
• Transduction, Genetic (radiation effects)
• Tumor Cells, Cultured (metabolism)
• Up-Regulation