1. ¹Department of Comparative Biomedical Sciences, Louisiana State University, Skip Bertman Drive, Baton Rouge, LA 70803, USA
2. ²Department of Neurosurgery, Henry Ford Health System, Detroit, MI 48083, USA
3. ³Department of Immunology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205-7199, USA

Correspondence: Shulin Li, E-mail: sli@vetmed.lsu.edu

Received 10 February 2005; Accepted 15 March 2005.

Abstract

Injection of DNA via electric pulses into targeted tissues is referred to as electrotransfer. Intratumoral electrotransfer of the IL12 gene is more effective than intramuscular electrotransfer of the same gene in the eradication of established tumors. To understand the underlying immunological mechanisms, T cell infiltration, CTL activity, inhibition of angiogenesis, and transgene expression were analyzed using immunohistochemistry, fluorescence-based CTL analysis, Northern blot, and ELISA. In addition, the therapeutic effects of IL12 gene therapy were determined in immunocompetent, immune-cell-depleted, and immunodeficient mice. We found that intratumoral, but not intramuscular, electrotransfer of the IL12 gene induces CD8⁺ T cell infiltration, CTL activity, and tumor eradication. Tumor eradication by intratumoral IL12 gene electrotransfer requires both NK and T cells. The absence of either cell type will abrogate the intratumoral IL12 gene therapy-induced tumor eradication. Such a requirement explains why tumors cannot be eradicated by intramuscular electrotransfer of the IL12 gene. Only NK-cell-dependent, and not T-cell-dependent, anti-tumor effects are induced by intramuscular administration. Together, these results suggest that NK cells play an important role in both administration routes, mediating tumor growth inhibition, but T cells are specifically activated by intratumoral IL12 gene electrotransfer and not by the intramuscular route.