Abstract | BACKGROUND: METHODS: A human glioma-derived cell culture (Ed147.BT) was transduced with B7-2, GM-CSF, and/or IL12 using retroviral vectors. Autologous peripheral blood mononuclear cells (PBMC) were co-cultured with irradiated gene-transduced tumor alone or a combination of radiated wild type and gene-transduced cells. Peripheral blood mononuclear cells proliferation was determined by serial cell counts. Peripheral blood mononuclear cells phenotype was assessed by flow cytometry for CD4, CD8, and CD16. Anti- tumor cytotoxicity was determined by chromium-51 (51Cr) release assay. RESULTS: Peripheral blood mononuclear cells cell numbers all decreased during primary stimulation but tumor cells expressing B7-2 or GM-CSF consistently caused secondary proliferation. Tumors expressing B7-2 and GM-CSF or B7-2, GM-CSF, and IL12 consistently increased PBMC CD8+ (cytotoxic T) and CD16+ (natural killer) percentages. Interestingly, anti- tumor cytotoxicity only exceeded that of PBMC stimulated with wild type tumor alone when peripheral blood mononuclear cells were stimulated with both wild type tumor and B7-2/ GM-CSF- (but not IL12) transduced cells. CONCLUSIONS: PBMC proliferation and phenotype is altered as expected by exposure to immunostimulatory gene-transduced tumor. However, transduced tumor cells alone do not stimulate greater anti- tumor cytotoxicity than wild type tumor. Only B7-2/ GM-CSF-transduced cells combined with wild type produced increased cytotoxicity. This may reflect selection of tumor subclones with limited antigenic spectra during retrovirus-mediated gene transfer.
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Authors | Ian F Parney, Maxine A Farr-Jones, Kevin Kane, Lung-Ji Chang, Kenneth C Petruk |
Journal | The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques
(Can J Neurol Sci)
Vol. 29
Issue 3
Pg. 267-75
(Aug 2002)
ISSN: 0317-1671 [Print] England |
PMID | 12195617
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Adjuvants, Immunologic
- Angiogenesis Inhibitors
- Antigens, CD
- B7-2 Antigen
- CD86 protein, human
- Cancer Vaccines
- Membrane Glycoproteins
- Interleukin-12
- Granulocyte-Macrophage Colony-Stimulating Factor
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Topics |
- Adjuvants, Immunologic
(genetics, therapeutic use)
- Angiogenesis Inhibitors
(genetics, therapeutic use)
- Antigens, CD
(genetics, therapeutic use)
- B7-2 Antigen
- Cancer Vaccines
(therapeutic use)
- Flow Cytometry
- Gene Transfer Techniques
- Genetic Therapy
(methods)
- Genetic Vectors
- Glioma
(genetics, immunology, therapy)
- Granulocyte-Macrophage Colony-Stimulating Factor
(genetics, therapeutic use)
- Humans
- Immunotherapy
(methods)
- Interleukin-12
(genetics, therapeutic use)
- Membrane Glycoproteins
(genetics, therapeutic use)
- Phenotype
- Transduction, Genetic
- Tumor Cells, Cultured
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