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Xenogeneic ICAM-1 gene transfer suppresses tumorigenicity and generates protective antitumor immunity
K Wei1, J G Wilson, C H Jurgensen
1Department of Cell Biology, Wellcome Research Laboratories, Research Triangle Park, NC 27709, USA.
Abstract:
Tumorigenicity in Fischer rats was not significantly reduced when the rat ICAM-1 gene was overexpressed in the rat tumor cell lines, JM-1 and SST-2. When these rat tumor cell lines were genetically modified with a gene encoding human ICAM-1, tumorigenicity was dramatically reduced. Expression of xenogeneic ICAM-1 did not alter the growth rate, expression of the major histocompatibility complex, nor morphological appearance of the cells. However, it did facilitate a tumor-specific immunological recognition and rejection of the genetically modified tumor cells. This effect resulted in a tumor-specific, long-term protective immunity directed against genetically unmodified tumor cells. Most importantly, administration of tumor cells genetically modified with genes encoding xenogeneic ICAM-1 can facilitate an immunological response to genetically unaltered pre-existing tumors. Transferring splenocytes from animals 'vaccinated' with the xenogeneic ICAM-1 gene altered tumor cells was able to transfer the antitumor response into recipient animals. Furthermore, transfer of CD8+ T lymphocytes produced the same result. These results suggested that tumors specific CD8+ T lymphocytes were activated by the xenogeneic altered tumor cells. THis activation generated the long-term, tumor-specific immunity.
Insights
Genetically modifying rat tumor cells with human ICAM-1 significantly reduced tumorigenicity. This approach also established long-term immunity against existing tumors, mediated by CD8+ T lymphocytes.
Area of Science:
- Immunology
- Oncology
- Gene Therapy
Background:
- Intercellular Adhesion Molecule-1 (ICAM-1) plays a role in immune responses.
- Understanding ICAM-1's function in tumor immunity is crucial for developing novel cancer therapies.
Purpose of the Study:
- To investigate the effect of xenogeneic (human) ICAM-1 gene transfer on the tumorigenicity of rat tumor cell lines.
- To determine if xenogeneic ICAM-1 expression can induce tumor-specific immunity and rejection.
Main Methods:
- Overexpression of rat ICAM-1 and human ICAM-1 in rat tumor cell lines (JM-1 and SST-2).
- Assessment of tumorigenicity, growth rate, major histocompatibility complex expression, and cell morphology.
- Evaluation of immunological recognition, rejection, and protective immunity in vivo.
- Adoptive transfer of splenocytes and CD8+ T lymphocytes from vaccinated animals.
Main Results:
- Overexpression of rat ICAM-1 did not reduce tumorogenicity.
- Genetic modification with human ICAM-1 dramatically reduced tumorogenicity.
- Xenogeneic ICAM-1 facilitated tumor-specific immune recognition and rejection.
- Induced long-term protective immunity against unmodified tumor cells and pre-existing tumors.
- Adoptive transfer of splenocytes and CD8+ T lymphocytes conferred anti-tumor response.
Conclusions:
- Xenogeneic ICAM-1 expression is a potent strategy for reducing tumor growth and inducing tumor-specific immunity.
- This approach activates tumor-specific CD8+ T lymphocytes, leading to long-term anti-tumor effects.
- Genetically modified tumor cells expressing xenogeneic ICAM-1 can serve as a vaccine to combat existing tumors.
