Abstract |
Because CD40 ligand ( CD40L) is a co-stimulator molecule for multiple components of the immune response, we wanted to determine whether transgenic expression of the molecule would increase immune responses against a weakly immunogenic murine tumor, neuro-2a. Tumor cells were transduced with a retroviral construct containing the CD40L gene and co-injected with variable numbers of non-CD40L transduced cells into syngeneic mice. Mice injected with cells that expressed CD40L had a significant reduction in average tumor size as compared to controls (p < 0.0001). In addition, survival of the neuro-2a/ CD40L mice was 48 days versus 34 days for the neuro-2a/neo controls (p < 0.02). Expression of CD40L by less than 1.5% of neuro-2a cells was sufficient for significant antitumor effects (p < 0.001). These antitumor effects protected mice from subsequent challenge with parental neuro-2a cells. The protective effects of CD40L were associated with systemic immunomodulation. In vivo depletion of CD8+ cells abrogated the CD40L-mediated antitumor effects. Analysis of spleens from CD40L-protected animals showed increased numbers of CD4+ and CD8+ cells, the majority of which co-expressed the activation marker CD25. In addition, an increased number of antigen-presenting cells (APCs) expressed the co-stimulatory molecule CD86. These experiments illustrate that transducing even a small percentage of tumor cells with CD40 ligand can create a long-lasting systemic immune response capable of impeding growth of unmodified neuroblastoma cells.
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Authors | M E Grossmann, M P Brown, M K Brenner |
Journal | Human gene therapy
(Hum Gene Ther)
Vol. 8
Issue 16
Pg. 1935-43
(Nov 01 1997)
ISSN: 1043-0342 [Print] United States |
PMID | 9382959
(Publication Type: Journal Article)
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Chemical References |
- Membrane Glycoproteins
- CD40 Ligand
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Topics |
- Animals
- Antigen-Presenting Cells
(immunology)
- CD4-Positive T-Lymphocytes
(immunology)
- CD40 Ligand
- CD8-Positive T-Lymphocytes
(immunology)
- Female
- Flow Cytometry
- Gene Expression Regulation, Neoplastic
- Gene Transfer Techniques
- Genetic Vectors
(genetics)
- Histocytochemistry
- Membrane Glycoproteins
(genetics, immunology)
- Mice
- Mice, Inbred A
- Neuroblastoma
(immunology, metabolism, therapy)
- Retroviridae
(genetics)
- Spleen
(cytology, immunology)
- Transgenes
- Tumor Cells, Cultured
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