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Successful immunogene therapy using colon cancer cells (colon 26) transfected with plasmid vector containing mature interleukin-18 cDNA and the Igκ leader sequence
- Source :
- Cancer Gene Therapy. 8:9-16
- Publication Year :
- 2001
- Publisher :
- Springer Science and Business Media LLC, 2001.
-
Abstract
- IL-18 is a novel cytokine that induces interferon (IFN)-gamma secretion and plays an important role in antitumor immunity. In the present study, we constructed plasmid vectors encoding the murine mature IL-18 cDNA linked with the Igkappa leader sequence and the pro-IL-18 cDNA to estimate the efficacy of the mature IL- 18 vector and to evaluate IL-18--producing tumor cells as a tumor vaccine. Colon 26 cells were transfected with the abovementioned vectors or with vector alone (mock). Reverse transcription-polymerase chain reaction analysis showed increased expression of murine IL-18 cDNA in both mature IL-18 and pro-IL-18 transfectants in comparison to that in mock transfected cells. The ability of the culture supernatants of mature IL-18 transfectants to induce IFN-gamma secretion was extremely high (40-140 pg/10(6) cells) in comparison to that of pro-IL-18 transfectants (4-18 pg/10(6) cells). When injected into syngeneic BALB/c mice, the growth of mature IL-18 transfectants, but not pro-IL-18 transfectants, was significantly less than that in mock transfected cells ( P< .01, by ANOVA and analysis of covariance). In addition, injection of colon 26 or Meth-A cells into mice immunized with a mature IL-18 transfectant revealed acquired immunity. Depletion of natural killer cells did not affect the growth of transfectants. However, the growth inhibitory effects were partially abrogated following treatment with anti-CD4+ and anti-CD8+ antibodies. These data suggest that the rejection of mature IL-18/colon 26 cells was mediated through T-cell activation. Gene therapy using mature IL-18 transfectants containing a plasmid vector and the Igkappa leader sequence may be a useful tumor vaccine.
- Subjects :
- Cancer Research
Fibrosarcoma
viruses
Genetic enhancement
medicine.medical_treatment
Gene Expression
Genes, MHC Class I
Immunoenzyme Techniques
Mice
Interferon
Tumor Cells, Cultured
Mice, Inbred BALB C
Membrane Glycoproteins
Reverse Transcriptase Polymerase Chain Reaction
Interleukin-18
Transfection
Acquired immune system
Killer Cells, Natural
Cytokine
CD4 Antigens
Colonic Neoplasms
embryonic structures
B7-1 Antigen
Molecular Medicine
medicine.drug
animal structures
CD8 Antigens
Recombinant Fusion Proteins
Genes, MHC Class II
Genetic Vectors
Immunoglobulins
Mice, Nude
Biology
Adenoviridae
Interferon-gamma
Antigen
Antigens, CD
Complementary DNA
medicine
Animals
Molecular Biology
DNA Primers
fungi
Genetic Therapy
Immunotherapy
Molecular biology
Immunoglobulin G
B7-2 Antigen
Neoplasm Transplantation
Subjects
Details
- ISSN :
- 14765500 and 09291903
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Cancer Gene Therapy
- Accession number :
- edsair.doi.dedup.....e01544707540e40f664cddea2ef7c9c9