Retrovirus-mediated gene transfer of the human gamma-IFN gene: a therapy for cancer.
A retroviral vector-mediated gene transfer system was used to introduce m gamma-IFN and h gamma-IFN genes into mouse and human tumor cells, respectively. Murine tumor cell lines and primary human melanoma tumor cells were successfully transduced with gamma-IFN vector, and these transduced cells secreted measurable levels of biologically active m gamma-IFN and h gamma-IFN, respectively. Both murine and human tumor cell lines that expressed gamma-IFN exhibited increased surface expression of HLA class I antigens when tested by Western blot and FACS analysis. gamma-IFN--transduced human melanoma cells were more active in stimulating tumor-specific cytolytic activity of CTLs from melanoma patients in vitro. m gamma-IFN--transduced tumor cells were substantially less tumorigenic than the corresponding parent tumor cell lines in immune-competent mice. In addition, injection of m gamma-IFN--transduced tumor cells resulted in activation of tumor-specific CTL in vivo. We plan to use gamma-IFN--transduced autologous tumor cells to boost host immune responses as a potential therapy for human melanoma.
Howard
B
B
Viagene, Inc., San Diego, California 92121.
Burrascano
M
M
McCallister
T
T
Chong
K
K
Gangavalli
R
R
Severinsson
L
L
Jolly
D J
DJ
Darrow
T
T
Vervaert
C
C
Abdel-Wahab
Z
Z
D000818:Animals; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000008:administration & dosage*; D008285:Major Histocompatibility Complex; D008545:Melanoma / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011994:Recombinant Proteins; D012190:Retroviridae / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
D006680:HLA Antigens; D011994:Recombinant Proteins; D007371:Interferon-gamma