Bernstein Michael B, Chakraborty Mala, Wansley Elizabeth K, Guo Zhimin, Franzusoff Alex, Mostböck Sven, Sabzevari Helen, Schlom Jeffrey, Hodge James W
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Vaccine. 2008 Jan 24;26(4):509-21. doi: 10.1016/j.vaccine.2007.11.033. Epub 2007 Dec 3.
Recombinant Saccharomyces cerevisiae (yeast) represents a unique and attractive vehicle to deliver antigens in vaccine immunotherapy protocols for cancer or infectious disease, in that it has been shown to be extremely safe and can be administered multiple times to hosts. In the studies reported here, we describe the effects of treatment with recombinant yeast on murine immature dendritic cells (DCs). Yeast expressing human carcinoembryonic antigen (CEA) as a model antigen was studied. Injection of mice subcutaneously with yeast-CEA resulted in rapid increases in MHC class II(+) cells and total antigen-presenting cells in draining lymph nodes. Post-treatment with yeast-CEA, DCs rapidly elevated both MHC class I and class II, numerous costimulatory molecules and other DC maturation markers, and secreted a range of Type I inflammatory cytokines. Gene expression arrays also revealed the rapid up-regulation of numerous cytokine and chemokine mRNAs, as well as genes involved in signal transduction and antigen uptake. Functional studies demonstrated enhanced allospecific reactivity of DCs following treatment with yeast-CEA or control yeast. Additionally, treatment of DCs with yeast-CEA resulted in specific activation of CEA-specific CD8(+) T cells in an MHC-restricted manner in vitro. Lastly, vaccination of CEA-transgenic mice with yeast-CEA elicited antigen-specific CD4(+) and CD8(+) immune responses in vivo. Thus, these studies taken together form a scientific rationale for the use of recombinant yeast in vaccination protocols for cancer or infectious diseases.
重组酿酒酵母（酵母）是癌症或传染病疫苗免疫治疗方案中递送抗原的一种独特且有吸引力的载体，因为它已被证明极其安全，并且可以多次给予宿主。在本文报道的研究中，我们描述了用重组酵母处理对小鼠未成熟树突状细胞（DCs）的影响。研究了表达人癌胚抗原（CEA）作为模型抗原的酵母。皮下注射酵母 - CEA的小鼠引流淋巴结中MHC II类（+）细胞和总抗原呈递细胞迅速增加。用酵母 - CEA处理后，DCs迅速上调MHC I类和II类、多种共刺激分子和其他DC成熟标志物，并分泌一系列I型炎性细胞因子。基因表达阵列还显示多种细胞因子和趋化因子mRNA以及参与信号转导和抗原摄取的基因迅速上调。功能研究表明，用酵母 - CEA或对照酵母处理后DCs的同种异体特异性反应性增强。此外，用酵母 - CEA处理DCs在体外以MHC限制的方式导致CEA特异性CD8（+）T细胞的特异性活化。最后，用酵母 - CEA对CEA转基因小鼠进行疫苗接种在体内引发了抗原特异性CD4（+）和CD8（+）免疫反应。因此，这些研究共同为重组酵母在癌症或传染病疫苗接种方案中的应用提供了科学依据。
