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Daqing Li, MD; Elizabeth Shugert, MD; Ming Guo, PhD; Jeffrey S. Bishop, MS; Bert W. O'Malley, Jr, MD

Arch Otolaryngol Head Neck Surg. 2001;127:1319-1324.

Objective  To determine the feasibility and efficacy of combination nonviral lipid-formulated murine interleukin 2 (mIL-2) and polymer-formulated murine interleukin 12 (mIL-12) gene therapy for head and neck squamous cell carcinoma (HNSCC) in a murine model.

Methods  Randomized, controlled studies in a murine HNSCC model. Tumors were established in the floor of mouth in C3H/HeJ immunocompetent mice. Established tumors were directly injected with lipid-formulated mIL-2 and polymer-formulated mIL-12 alone and in combination. Antitumor responses, cytokine expression, and natural killer cell and cytolytic T-lymphocyte activity were assayed.

Results  The use of combined mIL-2 and mIL-12 gene therapy resulted in significant antitumor effects, compared with each of the single-cytokine and no-treatment (control) groups (P = .01 to P = .02). Tumors treated with the formulated cytokine genes showed an increased level of the corresponding proteins and decreased level of transforming growth factor ß (TGF-ß) expression. Combined mIL-2 and mIL-12 treatment consistently produced the greater activation of cytolytic T-lymphocyte and natural killer cells than did single-cytokine treatment or other controls at all concentrations tested. Augmented immune responses correlated with clinical antitumor effects.

Conclusions  The nonviral gene delivery system was well tolerated, and combined mIL-2 and mIL-12 gene transfer generated potent antitumor immune responses against HNSCC in our murine model. Combined nonviral IL-2 and IL-12 gene therapy may have great potential as a primary or adjuvant treatment for HNSCC in humans.

From the Department of Otolaryngology–Head and Neck Surgery (Drs Li, Shugert, Guo, and O'Malley) and The Greenebaum Cancer Center (Drs Li and O'Malley), University of Maryland School of Medicine, Baltimore; and Valentis, Inc, The Woodlands, Tex (Mr Bishop). Dr O'Malley has a sponsored research agreement with equity options in Valentis, Inc.

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