Fong C L, Hui K M
Gene Vector Laboratory, Division of Cellular and Molecular Research, National Cancer Center, Singapore.
Gene Ther. 2002 Sep;9(17):1127-38. doi: 10.1038/sj.gt.3301783.
Dendritic cells (DC) are the most potent professional antigen-presenting cells with exquisite capacity to interact with T cells to initiate strong primary cellular immune responses. The antigen-presenting capability of DC makes them attractive vehicles for the delivery of therapeutic cancer vaccines. Recently, we have demonstrated that the introduction of a recombinant gene encoding the human Flt3L gene into mice could result in the expansion of the DC population in vivo. In this report, we have introduced the human Flt-3L gene via naked DNA-based immunization in combination with the muc-1 tumor peptide to immunize mice. We demonstrated that the population of DC expanded following stimulation with the human Flt-3L gene in vivo is functional and they are able to elicit potent muc-1 peptide-specific cellular responses. The strategy described here allows the efficient generation of antigen-specific CTL immunity in vivo and has the potential to be applied in developing efficient protocols for antigen-specific immunotherapy of human malignancies.
树突状细胞(DC)是最强大的专职抗原呈递细胞,具有与T细胞相互作用以启动强烈的原发性细胞免疫反应的精湛能力。DC的抗原呈递能力使其成为递送治疗性癌症疫苗的有吸引力的载体。最近,我们已经证明,将编码人Flt3L基因的重组基因导入小鼠体内可导致体内DC群体的扩增。在本报告中,我们通过基于裸DNA的免疫接种结合muc-1肿瘤肽来导入人Flt-3L基因以免疫小鼠。我们证明,体内经人Flt-3L基因刺激后扩增的DC群体具有功能,并且它们能够引发强效的muc-1肽特异性细胞反应。这里描述的策略允许在体内有效产生抗原特异性CTL免疫,并且有潜力应用于开发针对人类恶性肿瘤的抗原特异性免疫治疗的有效方案。