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Macrophage-based cell therapies: The long and winding road.

ABSTRACT: 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 (M?s) 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 M? 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 M?s. It is now known that while inflammatory M?s can kill tumor cells, the tumor environment is able to reprogram M?s 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 M?s, and how conditioning and gene engineering strategies are used to restrict the M? to an appropriate phenotype or to enable production of therapeutic proteins. We survey applications in which the M? is loaded with nanomedicines, such as liposomes ex vivo, so when the drug-loaded M?s are infused into an animal, the drug is released at the disease site. Finally, we also review the current status of M? biodistribution and survival after transplantation into an animal. The combination of these recent advances opens the way for improved M? cell therapies.

SUBMITTER: Lee S

PROVIDER: S-EPMC5064880 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Macrophage-based cell therapies: The long and winding road.

Lee Simon S Kivimäe Saul S Dolor Aaron A Szoka Francis C FC

Journal of controlled release : official journal of the Controlled Release Society 20160712

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 ...[more]

PMID: 27422609

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Macrophage-based cell therapies: The long and winding road.

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Macrophage-based cell therapies: The long and winding road.

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