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Retrovirus-mediated gene transfer of the human gamma-IFN gene: a therapy for cancer
B Howard1, M Burrascano, T McCallister
1Viagene, Inc., San Diego, California 92121.
Abstract:
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.
Insights
Gene transfer introduced gamma-interferon (IFN) genes into tumor cells, enhancing immune responses. This approach reduced tumor growth and increased anti-tumor activity, showing potential for melanoma therapy.
Area of Science:
- Immunology
- Oncology
- Gene Therapy
Background:
- Interferon-gamma (IFN) plays a crucial role in immune regulation and anti-tumor responses.
- Gene therapy offers a promising strategy for cancer treatment by modifying cellular functions.
Purpose of the Study:
- To investigate the efficacy of introducing mouse gamma-interferon (m gamma-IFN) and human gamma-interferon (h gamma-IFN) genes into tumor cells using retroviral vectors.
- To evaluate the impact of gamma-IFN expression on tumor cell characteristics, immune cell activity, and tumorigenicity.
Main Methods:
- Retroviral vector-mediated gene transfer was employed to introduce m gamma-IFN and h gamma-IFN genes into murine and human tumor cells, respectively.
- Transduced cells were analyzed for gamma-IFN secretion, surface HLA class I antigen expression (Western blot, FACS), and their effects on T-cell activity in vitro and in vivo.
Main Results:
- Successful transduction and secretion of biologically active m gamma-IFN and h gamma-IFN from respective tumor cells.
- Gamma-IFN expression led to increased surface HLA class I antigen expression on both murine and human tumor cells.
- Transduced human melanoma cells enhanced tumor-specific cytotoxic T lymphocyte (CTL) activity in vitro.
- M gamma-IFN-transduced murine tumor cells exhibited reduced tumorigenicity in vivo and activated tumor-specific CTL.
Conclusions:
- Gamma-IFN gene transfer into tumor cells can enhance anti-tumor immune responses by increasing HLA class I expression and stimulating CTL activity.
- Gamma-IFN-expressing tumor cells demonstrate reduced tumorigenicity and potential as a cellular immunotherapy for melanoma.
- The study supports the potential use of gamma-IFN-transduced autologous tumor cells to boost host immune responses for melanoma therapy.