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David Bray, MD; Shu-Zhen Yu, MD; Hilary Koprowski II, MA; Juong Rhee, PhD; Sanjeev Kumar, PhD; Federica Pericle, PhD; Mohan Suntharalingam, MD; David A. Van Echo, MD; Daqing Li, MD; Bert W. O'Malley, Jr, MD

Arch Otolaryngol Head Neck Surg. 2003;129:618-622.

Objectives  To demonstrate that the combination of nonviral murine interleukin 2 (mIL-2) gene therapy and external-beam radiation therapy (XRT) have an enhanced therapeutic effect for the treatment of head and neck squamous cell carcinoma (HNSCC) in an orthotopic murine model and to elucidate the mechanism of action.

Methods  Randomized, controlled studies in the murine orthotopic model of HNSCC. Squamous cell carcinoma VII cells were injected into the floor of the mouth to establish tumors in immunocompetent mice. The intervention groups were treated with mIL-2, radiation therapy, empty plasmid, no treatment, combination mIL-2/XRT, and combination empty plasmid/XRT. Nonviral mIL-2 gene transfer was performed on days 5 and 9. The XRT was administered to the assigned groups 24 hours after first mIL-2 delivery. The mice were killed on day 13. Tumors and local lymph nodes were harvested and evaluated. Primary and secondary cytokine expression, cytotoxic T-lymphocyte activity, and apoptosis were assayed.

Results  The combination mIL-2/XRT demonstrated a significant increase in antitumor effects compared with single therapy or controls. Increased expression levels of primary and secondary cytokines were found in the group treated with mIL-2, and this effect was preserved when mIL-2 treatment was combined with XRT. Combination therapy significantly increased apoptosis compared with monotherapy.

Conclusions  The present study demonstrates that combination mIL-2/XRT generates potent antitumor immune responses and significantly increases apoptosis in an orthotopic murine model of HNSCC. Further optimization of this strategy is warranted as well as consideration for human clinical trials.

From the Department of Otolaryngology–Head and Neck Surgery (Drs Bray, Yu, Li, and O'Malley and Mr Koprowski), The Greenebaum Cancer Center (Drs Suntharalingam, Van Echo, Li, and O'Malley), and Department of Radiation Oncology (Drs Rhee and Suntharalingam), University of Maryland School of Medicine, Baltimore; and Valentis Inc, The Woodlands, Tex (Drs Kumar and Pericle). Drs Kumar and Pericle are employed by Valentis Inc, a manufacturer of gene medicines for local and systemic therapy.

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