[Reduction of immunosuppression and shift to Th1 response by tumor-DC (dendritic cells) fusion vaccine].
Immunotherapy with tumor-dendritic cells (DC) fusion vaccine has been shown to induce an immune response against multiple tumor antigens including unknown tumor antigens. In this study, we examined immunological changes by tumor-DC fusion vaccine. Nine patients with advanced or recurrent gastrointestinal cancer that was unresponsive to standard surgical therapy and chemotherapy were enrolled in this study after informed consent was obtained. Monocytes were separated from the peripheral blood collected by leukapheresis, and were cultured with GM-CSF and IL-4 for 6 days. Then, TNF-alpha, IL-1beta, IL-6 and PGE2 were added for maturation of DC. Fusion of irradiated tumor cells and DC was created by polyethylene glycol and electroporation. The fusion vaccine was injected subcutaneously into the inguinal region four times every two weeks. There were no adverse effects or autoimmune responses after vaccination in any patients. The clinical response was stable in five patients, and disease progression in four patients. Delayed skin tests changed to positive in six of the nine patients after vaccination. IAP levels decreased in five patients and TGF-beta levels decreased in six patients. Th1/Th2 and Tc1/Tc2 balances improved in six of the nine patients after vaccination. In this study, it was shown that immunosuppressive factors, such as IAP and TGF-beta, and Th1 balance are useful as markers of immunomonitoring for tumor-DC fusion vaccine in patients with advanced or recurrent gastrointestinal patients.
Iinuma
Hisae
H
Dept. of Surgery, Teikyo University School of Medicine.
Okinaga
Kota
K
Fukushima
Ryoji
R
Inaba
Tsuyoshi
T
Iwasaki
Kota
K
Arai
Takekazu
T
Tamura
Junko
J
Kumagai
Harumi
H
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects; D002459:Cell Fusion; D003713:Dendritic Cells / Q000276:immunology*; D018274:Electroporation; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008297:Male; D008875:Middle Aged; D014611:Vaccination
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines