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Retrovirus‐Mediated Gene Transfer of the Human γ‐IFN Gene: A Therapy for Cancer
Author(s) -
HOWARD BRAD,
BURRASCANO MICHELLE,
McCALLISTER TAMMY,
CHONG KIM,
GANGAVALLI RAMARAO,
SEVERINSSON LIV,
JOLLY DOUGLAS J.,
DARROW TIMOTHY,
VERVAERT CAROL,
ABDELWAHAB ZEINHAB,
SIEGLER HILLIARD F.,
BARBER JACK R.
Publication year - 1994
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1994.tb21711.x
Subject(s) - melanoma , genetic enhancement , ctl* , cancer research , immune system , interferon gamma , cell culture , biology , immunotherapy , viral vector , cytolysis , immunology , in vitro , microbiology and biotechnology , cytotoxic t cell , gene , recombinant dna , biochemistry , genetics , cd8
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.