Macrophage-based cell therapies: The long and winding road.
Macrophage-based cell therapies: The long and winding road.
复制标题
DOI：
10.1016/j.jconrel.2016.07.018
复制
发表时间：
2016-10-28
期刊：
影响因子：
--
通讯作者：
Szoka FC
中科院分区：
文献类型：
--
作者：
Lee S;Kivimäe S;Dolor A;Szoka FC
在寻找更好的药物的过程中，人们越来越多地将注意力转向基于细胞的疗法。其基本原理是，注入细胞可以提供一种靶向治疗，以精确纠正复杂的疾病表型。1987年至2010年间，自体巨噬细胞（MΦs）被用于临床试验，治疗多种人类肿瘤；这种方法在一些患者中提供了适度的治疗益处，但没有持久的缓解。这些试验是在了解MΦ表型的复杂性，它们根据各种细胞因子和/或环境改变其表型的能力以及重新注入MΦs的存活程度之前启动的。现在我们知道，虽然炎症MΦs可以杀死肿瘤细胞，但肿瘤环境能够将MΦs重新编程为致瘤表型；诱导血管形成和促进癌细胞生长的环境。我们回顾了新信息如何使大量离体生成MΦs的发展成为可能，以及如何使用条件调节和基因工程策略将MΦ限制为适当的表型或使治疗性蛋白质的生产成为可能。我们调查了MΦ装载纳米药物的应用，例如体外脂质体，因此当将装载药物的MΦs注入动物体内时，药物在疾病部位释放。最后，我们也回顾了MΦ在动物体内移植后的生物分布和存活的现状。这些最新进展的结合为改进MΦ细胞疗法开辟了道路。
In the quest for better medicines, attention is increasingly turning to cell-based therapies. The rationale is that infused cells can provide a targeted therapy to precisely correct a complex disease phenotype. Between 1987 and 2010, autologous macrophages (MΦs) were used in clinical trials to treat a variety of human tumors; this approach provided a modest therapeutic benefit in some patients but no lasting remissions. These trials were initiated prior to an understanding of: the complexity of MΦ phenotypes, their ability to alter their phenotype in response to various cytokines and/or the environment, and the extent of survival of the re-infused MΦs. It is now known that while inflammatory MΦs can kill tumor cells, the tumor environment is able to reprogram MΦs into a tumorigenic phenotype; inducing blood vessel formation and contributing to a cancer cell growth-promoting milieu. We review how new information enables the development of large numbers of ex vivo generated MΦs, and how conditioning and gene engineering strategies are used to restrict the MΦ to an appropriate phenotype or to enable production of therapeutic proteins. We survey applications in which the MΦ is loaded with nanomedicines, such as liposomes ex vivo, so when the drug-loaded MΦs are infused into an animal, the drug is released at the disease site. Finally, we also review the current status of MΦ biodistribution and survival after transplantation into an animal. The combination of these recent advances opens the way for improved MΦ cell therapies.
登录
查看更多内容
影响因子：
5
作者：
Bressani RF;Nowacek AS;Singh S;Balkundi S;Rabinow B;McMillan J;Gendelman HE;Kanmogne GD
通讯作者：
Kanmogne GD
使用细胞木马马将纳米颗粒传递到乳腺癌的脑转移量。
影响因子：
5.7
作者：
Choi MR;Bardhan R;Stanton-Maxey KJ;Badve S;Nakshatri H;Stantz KM;Cao N;Halas NJ;Clare SE
通讯作者：
Clare SE
影响因子：
4.1
作者：
BURKE, AM;QUEST, DO;CERRI, C
通讯作者：
CERRI, C
影响因子：
10.8
作者：
Champion, Julie A.;Katare, Yogesh K.;Mitragotri, Samir
通讯作者：
Mitragotri, Samir
影响因子：
4.7
作者：
Batrakova, Elena V.;Li, Shu;Gendelman, Howard E.
通讯作者：
Gendelman, Howard E.