Meng Shuhan, Whitt Aaron G, Eaton John W, Yaddanapudi Kavitha, Li Chi
Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, USA.
Experimental Therapeutics Group, Brown Cancer Center, Department of Medicine, University of Louisville, Louisville, KY, USA.
Sci Rep. 2024 Dec 30;14(1):32127. doi: 10.1038/s41598-024-83932-0.
Based on the antigenic similarity between tumor cells and embryonic stem cells (ESCs), several recent studies report the use of intact murine ESCs or exosomes from murine ESCs as cancer vaccines. Since the capacity for self-renewal is one of the most specialized properties shared between ESCs and a subset of tumor cells, cancer stem cells (CSCs), we investigated whether the undifferentiated state of murine ESCs is essential for the prophylactic effectiveness of an ESC-based vaccine. The undifferentiated state of ES-D3, a murine ESC line, was essential for their anchorage-independent growth potential. Importantly, differentiation of ES-D3 cells decreased their efficacy in preventing the outgrowth of implanted lung tumors. Furthermore, the long-term cancer-preventive potential of this vaccine was also inhibited by the differentiation of these cells. To examine the antigenicity of the ESC-derived vaccine, we performed combined affinity chromatography shotgun immunoproteomic experiments to identify antigens specific to the whole-cell ES vaccine as well as to the ESC-derived exosome vaccine. Our data demonstrate that antibodies against several lung cancer-associated keratin members were enriched in the serum of vaccinated mice. In summary, these data suggest that the tumor-preventing efficacy of ESC-based vaccine is reliant on the differentiation properties of these stem cells.
基于肿瘤细胞与胚胎干细胞（ESCs）之间的抗原相似性，最近的几项研究报道了使用完整的小鼠胚胎干细胞或来自小鼠胚胎干细胞的外泌体作为癌症疫苗。由于自我更新能力是胚胎干细胞和一部分肿瘤细胞（即癌症干细胞，CSCs）共有的最特殊特性之一，我们研究了小鼠胚胎干细胞的未分化状态对于基于胚胎干细胞的疫苗的预防效果是否至关重要。小鼠胚胎干细胞系ES-D3的未分化状态对于其不依赖贴壁的生长潜能至关重要。重要的是，ES-D3细胞的分化降低了它们预防植入性肺肿瘤生长的效果。此外，这些细胞的分化也抑制了这种疫苗的长期癌症预防潜能。为了检测胚胎干细胞衍生疫苗的抗原性，我们进行了组合亲和层析鸟枪法免疫蛋白质组学实验，以鉴定全细胞胚胎干细胞疫苗以及胚胎干细胞衍生外泌体疫苗特有的抗原。我们的数据表明，接种疫苗小鼠的血清中富集了针对几种肺癌相关角蛋白成员的抗体。总之，这些数据表明基于胚胎干细胞的疫苗的肿瘤预防效果依赖于这些干细胞的分化特性。
