Duke University Medical Center, Department of Surgery, Box 103035, Durham, NC 27710, USA.
Expert Opin Biol Ther. 2010 Apr;10(4):563-74. doi: 10.1517/14712591003614749.
Although studies have demonstrated that antigen-loaded dendritic cells (DC) elicit antigen-specific immune responses, the clinical benefit from DC-based cancer immunotherapy remains low. RNA, in the form of mRNA, has not only been used as a source of antigen but more recently as a way to stimulate DC to produce immunostimulatory molecules. As siRNA it has allowed researchers to modify DC to produce a favorable cytokine profile or to present antigen that may generate the desired immune response.
When loading DC with RNA that encodes immunostimulatory protein, rather than a source of antigen, optimal translation and efficient transfection into DC are critical. Studies addressing these issues and the functional consequences of modulating DC function are reviewed.
RNA can be used to load DC with antigen and to encode proteins that will enhance the immune response. Co-transfection with multiple mRNAs or mRNA plus siRNA can significantly improve vaccine efficacy.
One conclusion from Phase I clinical trials with DC loaded with tumor antigen is that tumor-specific induction of immune responses is not sufficient to destroy pre-established tumors. The advantage of transfection with mRNA is the ability to load DC with antigen-encoding mRNA and immunostimulatory protein-encoding mRNA to achieve the desired clinical response.
尽管研究表明负载抗原的树突状细胞 (DC) 可引发抗原特异性免疫反应，但基于 DC 的癌症免疫疗法的临床获益仍然较低。RNA 不仅以前被用作抗原的来源，最近还被用作刺激 DC 产生免疫刺激分子的一种方式。作为 siRNA，它使研究人员能够修饰 DC 以产生有利的细胞因子谱，或呈递可能引发所需免疫反应的抗原。
当用编码免疫刺激蛋白的 RNA 而非抗原来源负载 DC 时，最佳翻译和有效转染到 DC 至关重要。本文综述了解决这些问题以及调节 DC 功能的功能后果的研究。
RNA 可用于负载 DC 抗原，并编码可增强免疫反应的蛋白。同时转染多种 mRNA 或 mRNA 加 siRNA 可以显著提高疫苗的功效。
肿瘤抗原负载的 DC 的 I 期临床试验得出的一个结论是，肿瘤特异性诱导的免疫反应不足以破坏预先建立的肿瘤。用 mRNA 转染的优势在于能够用编码抗原的 mRNA 和编码免疫刺激蛋白的 mRNA 负载 DC，以实现预期的临床反应。
