Combination nonviral cytokine gene therapy for head and neck cancer.
OBJECTIVE
To establish the feasibility and efficacy of combination nonviral murine interferon-alpha (mIFN-alpha)and murine interleukin-2 (mIL-2) or murine interleukin-12 (mIL-12) gene therapy for head and neck squamous cell carcinoma in a murine model.


METHODS
Randomized controlled studies in a murine head and neck cancer model were performed to assess antitumor responses, secondary cytokine expression, and both natural killer (NK) cell and cytolytic T-cell (CTL) activity.


METHODS
Tumors were established in the floor of mouth in C3H/HeJ immunocompetent mice. Established tumors were directly injected with polymer-formulated murine interferon-alpha (mIFN-alpha), lipid-formulated mIL-2, and polymer-formulated mIL-12 alone or in combination. Primary and secondary cytokine expression,NK cell activity, and CTL activity were assayed.


RESULTS
The use of mIFN-alpha gene therapy in combination with either mIL-2 or mIL-12 resulted in significant antitumor effects as compared with each of the single cytokine and control treatment groups (P = .002). Increased levels of NK cell activity and tumor specific CD8+ cytotoxic T-lymphocyte activity were found in the combination mIFN-alpha and mIL-2 or mIL-12 groups. Augmented immune responses correlated with clinical antitumor effects.


CONCLUSIONS
The present study demonstrates that mIL-2 or mIL-12 augments tumor inhibition from mIFN-alpha and increases activation of NK and CD8+ T cells. These data support further investigation of polymer and lipid mediated delivery of cytokine genes for head and neck cancer.
Li
D
D
Department of Otolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, 16 South Eutaw Street, Baltimore, MD 21201, USA.
Zeiders
J W
JW
Liu
S
S
Guo
M
M
Xu
Y
Y
Bishop
J S
JS
O'Malley
B W
BW
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D004195:Disease Models, Animal; D005240:Feasibility Studies; D015316:Genetic Therapy / Q000379:methods*; D006258:Head and Neck Neoplasms / Q000628:therapy*; D016898:Interferon-alpha / Q000032:analysis / Q000235:genetics*; D018664:Interleukin-12 / Q000032:analysis / Q000235:genetics*; D007376:Interleukin-2 / Q000032:analysis / Q000235:genetics*; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D010957:Plasmids; D011897:Random Allocation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D016898:Interferon-alpha; D007376:Interleukin-2; D018664:Interleukin-12