Marked enhancement of antitumor immune responses in mouse brain tumor models by genetically modified dendritic cells producing Semliki Forest virus-mediated interleukin-12.
| Autor: | Yamanaka R; Clinical Gene Therapy Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA. ryaman@pop11.odn.ne.jp, Zullo SA, Ramsey J, Yajima N, Tsuchiya N, Tanaka R, Blaese M, Xanthopoulos KG |
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| Jazyk: | angličtina |
| Zdroj: | Journal of neurosurgery [J Neurosurg] 2002 Sep; Vol. 97 (3), pp. 611-8. |
| DOI: | 10.3171/jns.2002.97.3.0611 |
| Abstrakt: | Object: The authors evaluated dendritic cell (DC)-based immunotherapy for malignant brain tumor to improve its therapeutic efficacy. Methods: Dendritic cells were isolated from bone marrow and pulsed with phosphate-buffered saline, Semliki Forest virus (SFV)-LacZ, retrovirus vector GCsap-interleukin (IL)-12, and SFV-IL-12, respectively, to treat mice bearing brain tumors of the B16 cell line. The results indicated that therapeutic immunization with DCs pulsed with SFV-IL-12 prolonged the survival of mice with established tumors. Semliki Forest virus induced apoptosis in DCs, which in turn facilitated the uptake of apoptotic cells by other DCs, thus providing a potential mechanism for enhanced immunogenicity. Conclusions: Therapy with DCs that have been pulsed with SFV-mediated IL-12 may be an excellent step in the development of new cancer vaccines. Intratumorally injected DCs that have been transiently transduced with IL-12 do not require pulsing of a source of tumor antigens to induce tumor regression. |
| Databáze: | MEDLINE |
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