Combination nonviral interleukin 2 and interleukin 12 gene therapy for head and neck squamous cell carcinoma.
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 beta (TGF-beta) 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.
Li
D
D
Department of Otolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, USA.
Shugert
E
E
Guo
M
M
Bishop
J S
JS
O'Malley
B W
BW
D000276:Adjuvants, Immunologic / Q000235:genetics / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000276:immunology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000276:immunology; D015552:Injections, Intralesional; D018664:Interleukin-12 / Q000235:genetics* / Q000276:immunology / Q000627:therapeutic use; D007376:Interleukin-2 / Q000235:genetics* / Q000276:immunology / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D010957:Plasmids; D018709:Statistics, Nonparametric; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D007376:Interleukin-2; D018664:Interleukin-12