The experimental study of ovarian carcinoma vaccine modified by human B7-1 and IFN-gamma genes.
With the advance of immunology, immunogene therapy is becoming a possible therapeutic alternative to advanced cancer. The aim of tumor immunogene therapy is to enhance the immune response to tumors. Evidence suggests that CD80 (B7-1) and Interferon-gamma (IFN-gamma) play important roles in antitumor immunity induced by T lymphocyte. To study the antitumor immune effects of ovarian carcinoma vaccine modified with human B7-1 and IFN-gamma genes, we constructed the bicistronic retroviral vector pLXSN, encoding human B7-1 and IFN-gamma. In vitro, the primary ovarian carcinoma cells were transduced with the retroviral vector and prepared as a vaccine. Then autologous lymphocytes were irritated with the ovarian carcinoma cells for competition inhibitory cytotoxic testing. The tumor-specific cytotoxic activity was greatly enhanced by the double gene-modified vaccine. In vivo, the tumorigenicity of the double gene-modified ovarian cell line 3AO/B7-1.IFN-gamma was evaluated in a human immune reconstituted SCID mice (hu-PBL-SCID) model. The double-gene modification markedly decreases tumor genecity. Together, the results suggest that combining B7-1 and IFN-gamma could be a useful therapeutic approach in ovarian cancer.
Qian
H-N
HN
Gynecologic Oncology Center, Peking University People's Hospital, Beijing 100044, China. shemp@public.bta.net.cn
Liu
G-Z
GZ
Cao
S-J
SJ
Feng
J
J
Ye
X
X
D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics* / Q000378:metabolism; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002455:Cell Division / Q000502:physiology; D005260:Female; D005805:Genes, MHC Class I / Q000502:physiology; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012190:Retroviridae / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D014162:Transfection / Q000379:methods; D014407:Tumor Cells, Cultured
D018122:B7-1 Antigen; D019496:Cancer Vaccines; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma