Vaccination with Human Pluripotent Stem Cells Generates a Broad Spectrum of Immunological and Clinical Responses Against Colon Cancer
Vaccination with Human Pluripotent Stem Cells Generates a Broad Spectrum of Immunological and Clinical Responses Against Colon Cancer
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DOI：
10.1002/stem.234
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发表时间：
2009-12-01
期刊：
影响因子：
5.2
通讯作者：
Li, Zihai
中科院分区：
文献类型：
--
作者：
Li, Yi;Zeng, Hui;Li, Zihai
用胚胎材料进行免疫以产生抗肿瘤免疫反应的历史可以追溯到一个世纪前。前提是癌细胞与胚胎材料共享癌胎儿抗原的表达，并且胚胎组织中针对这些抗原的免疫反应对癌症具有交叉保护作用。然而，由于缺乏统一的来源组织和伦理挑战，这种做法从未超越实验动物环境。随着具有良好特性的人类多能干细胞的出现，现在人们可能会问，干细胞是否真的能激发肿瘤保护性免疫。在这里，我们调查了特定的人类胚胎干细胞(HESCs)或诱导的多能干细胞(IPS)疫苗是否对结肠癌有效。我们发现hESC株H9免疫小鼠产生了一致的抗CT26结肠癌的细胞和体液免疫反应。保护与肿瘤反应和干扰素-c产生细胞的扩张以及脾中CD11b(+)Gr-1(+)髓系来源抑制细胞的严重丧失密切相关。没有观察到自身免疫的证据。我们还比较了在同一干细胞设施中产生的hESC系CT2和iPS细胞系TZ1对结肠癌的免疫原性。我们发现iPS细胞株在提供肿瘤保护作用方面不如hESC细胞系，提示hESCs和iPS细胞表达的癌胎儿抗原存在异质性。我们认为，基于hESC的疫苗是一种很有前途的肿瘤免疫治疗方法。干细胞2009；27：3103-3111
The history of immunizing with embryonic materials to generate an antitumor immune response dates back to a century ago. The premise is that cancer cells share the expression of oncofetal antigens with embryonic materials and that the immune response against these antigens in the embryonic tissues is cross-protective against cancer. However, such a practice has never advanced beyond experimental animal settings, because of lack of uniformed source tissues and ethical challenges. With the availability of well-characterized human pluripotent stem cells, it is now possible to ask whether tumor protective immunity could indeed be elicited with stem cells. Herein, we investigated whether vaccination with defined human embryonic stem cells (hESCs) or induced pluripotent stem (iPS) cells was effective against a colon carcinoma. We discovered that vaccination of mice with hESC line H9 generated consistent cellular and humoral immune responses against CT26 colon carcinoma. Protection correlated strongly with the expansion of tumor-responsive and interferon-c-producing cells and the profound loss of CD11b(+)Gr-1(+) myeloid-derived suppressor cells in the spleen. No evidence of autoimmunity was observed. We also compared the immunogenicity against colon cancer between a hESC line CT2 and an iPS cell line TZ1 that were generated in the same stem cell facility. We found that the iPS cell line was inferior to the hESC line in conferring tumor protection, suggesting that there is heterogeneity of expression of oncofetal antigens by hESCs and iPS cells. We conclude that the hESC-based vaccine is a promising modality for immunotherapy of cancer. STEM CELLS 2009;27:3103-3111