Gene therapy for head and neck cancer using vaccinia virus expressing IL-2 in a murine model, with evidence of immune suppression.
We evaluated the efficiency of recombinant vaccinia virus expressing interleukin-2 (rvv-IL-2) as a tumor vaccine in an immunocompetent mouse model of head and neck squamous cell carcinoma (SCC VII/SF). Mice with five-day-old tumors in the floor of the mouth were treated with rvv-IL-2 by intratumoral injections. These treated mice survived longer (P <.03) than mice treated with control vaccines. Splenocytes, bone marrow, and lymph node cells from tumor-bearing mice responded poorly to concanavalin A stimulation, suggesting induction of immunosuppression. The rvv-IL-2 virus grew for 7 days in the tumor following intratumoral injection. We did not detect any virus particles in several normal organs following rvv-IL-2 injection. Comparison of expression levels of several potential immune inhibitory mediators between the tumors growing in mice and cultured tumor cells demonstrated higher expression of IL-10, GM-CSF, TGF-beta, and NO synthetase in tumors. These results suggested possible roles for these molecules in immunosuppression. We conclude that rvv-IL-2 has potential as a therapeutic vaccine for head and neck cancer and that it can be more effective provided the immunosuppression is reversed.
Qin
H
H
Department of Internal Medicine and the Barrett Cancer Center, University of Cincinnati, Cincinnati, Ohio 45267, USA.
Valentino
J
J
Manna
S
S
Tripathi
P K
PK
Bhattacharya-Chatterjee
M
M
Foon
K A
KA
O'Malley
B W
BW
Chatterjee
S K
SK
D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000628:therapy*; D003208:Concanavalin A / Q000494:pharmacology; D017931:DNA Primers / Q000737:chemistry; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D009368:Neoplasm Transplantation; D019001:Nitric Oxide Synthase / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014616:Vaccinia virus / Q000502:physiology*
D017931:DNA Primers; D007376:Interleukin-2; D016212:Transforming Growth Factor beta; D003208:Concanavalin A; D016753:Interleukin-10; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019001:Nitric Oxide Synthase