來自美國和中國的科學(xué)家在《干細(xì)胞》雜志上發(fā)表的一項(xiàng)研究中說,,他們發(fā)現(xiàn)了人類干細(xì)胞具有提供結(jié)腸癌疫苗的潛力,。
由免疫學(xué)專家Bei Liu 博士和 Zihai Li博士領(lǐng)導(dǎo)的這項(xiàng)發(fā)現(xiàn)是建立在具有一個(gè)世紀(jì)的歷史的一項(xiàng)理論之上的,,即用胚胎物質(zhì)進(jìn)行免疫接種可能產(chǎn)生一種抗腫瘤應(yīng)答,。然而,,這種理論從未超出過動(dòng)物研究,,因此這項(xiàng)關(guān)于人類干細(xì)胞可以用于預(yù)防結(jié)腸癌的免疫接種的發(fā)現(xiàn)既新又令人意外。
“這項(xiàng)發(fā)現(xiàn)有潛力為癌癥疫苗研究打開一個(gè)新的范式,,”Zihai Li博士說,。“癌和干細(xì)胞同樣擁有許多分子和生物特征,。通過用干細(xì)胞為宿主接種,我們有能力‘欺騙’免疫系統(tǒng)認(rèn)為癌細(xì)胞存在,,因此也就啟動(dòng)了一個(gè)抗癌免疫程序,。”
該研究是首個(gè)涉及人類干細(xì)胞在預(yù)防結(jié)腸癌的免疫接種方面的研究,,而且代表了Zihai Li博士與干細(xì)胞專家Renhe Xu在康涅狄格大學(xué)干細(xì)胞研究所的著名實(shí)驗(yàn)室之間的合作,。
這個(gè)研究組用人類胚胎干細(xì)胞(hES)為實(shí)驗(yàn)室小鼠進(jìn)行的免疫接種,,并發(fā)現(xiàn)了針對結(jié)腸癌的持續(xù)的免疫應(yīng)答,。該研究組見到了接受免疫的小鼠的腫瘤生長顯著減少,。這顯示了接受免疫接種的小鼠可能通過應(yīng)用hES細(xì)胞從而產(chǎn)生強(qiáng)有力的抗腫瘤應(yīng)答。
該研究組還發(fā)現(xiàn),,盡管天然的胚胎干細(xì)胞有能力產(chǎn)生應(yīng)答,人造的誘導(dǎo)多能干細(xì)胞(iPSC)卻不能,。這很重要,因?yàn)樗魬?zhàn)了一種理論,,即iPSC 和hES一樣,、而且可能在干細(xì)胞研究的前沿領(lǐng)域代替后者,。
“盡管我們僅僅測試了對結(jié)腸癌的保護(hù)作用,,我們認(rèn)為干細(xì)胞可能有助于產(chǎn)生廣譜抗癌免疫應(yīng)答,,因此可以作為一種通用的癌癥疫苗,。”Bei Liu博士得出結(jié)論說。(生物谷Bioon.com)
生物谷推薦原始出處:
STEM CELLS DOI:10.1002/stem.234
Vaccination with Human Pluripotent Stem Cells Generates a Broad Spectrum of Immunological and Clinical Response against Colon Cancer
Yi Li 1 4, Hui Zeng 2 3 5, Ren-He Xu 2 3, Bei Liu 1 2 *, Zihai Li 1 2 *
1Department of Immunology, University of Connecticut School of Medicine, Farmington, CT 06030-1601
2UConn Stem Cell Institute, University of Connecticut School of Medicine, Farmington, CT 06030-1601
3Department of Genetics and Developmental Biology, University of Connecticut School of Medicine, Farmington, CT 06030-1601
4Department of Gynecology and Obstetrics, Peking University People's Hospital, 100044 Beijing, China
5Department of Hematology, Xiang-Ya Hospital, Central South University, Changsha, Hunan 410008, China
The history of immunizing with embryonic materials to generate an anti-tumor immune response dates back 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, due to lack of uniformed source tissues and ethical challenges. With the availability of well-characterized human pluripotent stem cells, it is now possible to ask if tumor protective immunity could indeed be elicited with stem cells. Herein, we investigated if vaccination with defined human embryonic stem (hES) or induced pluripotent stem (iPS) cells was effective against a colon carcinoma. We discovered that vaccination of mice with hES cell line H9 generated consistent cellular and humoral immune responses against CT26 colon carcinoma. Protection correlated strongly with the expansion of tumor-responsive and interferon -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 hES cell 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 hES cell line in conferring tumor protection, suggesting that there is heterogeneity of expression of oncofetal antigens by hES and iPS cells. We conclude that the hES-based vaccine is a promising modality for immunotherapy of cancer.