[Combination radiation and gene therapy for head and neck squamous cell carcinoma in the murine model].

OBJECTIVE

To examine the antitumour efficacy and investigate immunological mechanism of combination therapy of IL-2 gene and IL-12 gene transfer with radiation in an immunocompetent murine model that parallel more closely the clinical therapy of head and neck squamous cell carcinoma (HNSCC).

METHODS

Tumors were established in the floor of mouth in C3H/HeJ mice with SCCVII cell line. Lipid-DNA complexed (lipoplexes) by using polycationic liposome-Mediated transduction for HNSCC was transduced in tumor-bearing mouse by direct intratumoral gene transfer. The local tumor was radiated with a dose of 2 Gy in the second day. Tumor sizes were measured before and after the treatment as compared to the different single treatment groups and the controls. After tumors were subculture, the supernatants were collected for IL-2 and IL-12 expression by enzyme-linked immunosorbent assay (ELISA). Natural killer (NK) cell activity and cytotoxic T-lymphocyte (CTL) activity were also assayed by LDH method. CD4+ and CD8+ T-lymphocyte in tumor tissues were examined by immunohistochemistry.

RESULTS

HNSCC tumor growth was significantly inhibited following combined IL-2 and IL-12 gene therapy with radiation as compared to IL-2 or IL-12 gene therapy with radiation, single IL-2 or IL-12 gene therapy, radiation alone and the controls. Increased secreted levels of IL-2 and IL-12 protein expression were found in combined and single IL-2 gene or IL-12 gene treated groups. The combination and single gene treated groups produced greater activation of CTL and NK than the controls of all concerned test. The significant CD4+ and CD8+ T lymphocyte infiltration was distributed and the numerous necrosis were seen in tumor tissues after combination therapy.

CONCLUSIONS

Combined IL-2 gene and IL-12 gene therapy with radiation could significantly inhibited HNSCC tumor growth in the murine model and efficiently induced antitumor immunity of the host.