Immunotherapy with iPSC-derived dendritic cells brings a new perspective to an old debate: autologous versus allogeneic?
Immunotherapy with iPSC-derived dendritic cells brings a new perspective to an old debate: autologous versus allogeneic?
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DOI：
10.18609/cgti.2019.062
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发表时间：
2019-07
期刊：
影响因子：
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通讯作者：
P. Fairchild;T. J. Davies;C. Horton;K. Shanmugarajah;M. Bravo
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文献类型：
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作者：
P. Fairchild;T. J. Davies;C. Horton;K. Shanmugarajah;M. Bravo
诱导多能性的出现已经提高了基于从患者自身的体细胞衍生诱导多能干细胞（iPSC）的个体化疗法的前景。这种定制的细胞产品可以成功地规避受者免疫系统的排斥问题，但也提出了可负担性、产生患者特异性细胞系的成本及其随后在cGMP条件下分化的问题，证明了这是一种具有挑战性的商业模式。然而，在考虑从iPSC分化的树突状细胞（DC）的治疗用途时，过去指导自体和同种异体细胞产品之间的决定的原则可能证明不太可靠，iPSC在免疫系统中的作用在完全同种异体环境中会受到不利影响。在这里，我们回顾了为自体和同种异体细胞疗法之间的争论提供信息的免疫学概念，并讨论最近的突破是否可能为这个长期存在的问题提供新的解决方案，为广泛采用基于DC的免疫疗法铺平道路，并增加其从免疫肿瘤学（IO）到诱导免疫耐受的范围。
The advent of induced pluripotency has raised the prospect of personalized therapies based on the derivation of induced pluripotent stem cells (iPSC) derived from a patient’s own somatic cells. Such bespoke cell products may successfully circumvent issues of rejection by the recipient’s immune system but raise questions of affordability, the costs of generating patient-specific cell lines and their subsequent differentiation under cGMP conditions, proving a challenging business model. However, principles that have guided the decision between autologous and allogeneic cell products in the past may prove less reliable when considering the therapeutic use of dendritic cells (DC) differentiated from iPSC, whose role in the immune system would be adversely compromised in a fully allogeneic setting. Here, we review the immunological concepts that inform the debate between autologous and allogeneic cell therapies and discuss whether recent breakthroughs might provide a novel solution to this long-standing issue, paving the way for the widespread adoption of DC-based immunotherapy and increasing its reach from immune oncology (IO) to the induction of immunological tolerance.