4.6 Review

Emerging local immunomodulatory strategies to circumvent systemic immunosuppression in cell transplantation

Journal

EXPERT OPINION ON DRUG DELIVERY
Volume 19, Issue 5, Pages 595-610

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1080/17425247.2022.2076834

Keywords

Local immunosuppression; cell therapy; immunomodulation; long-acting drug delivery

Funding

  1. Juvenile Diabetes Research Foundation [JDRF 2-SRA-2021-1078-S-B]
  2. Vivian L. Smith Foundation

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This article reviews recent advances in immunoengineering strategies for localized immunomodulation, aiming to support allograft function and provide immune tolerance in a safe and effective manner.
Introduction Cell transplantation is a promising curative therapeutic strategy whereby impaired organ function can be restored without the need for whole-organ transplantation. A key challenge in allotransplantation is the requirement for life-long systemic immunosuppression to prevent rejection, which is associated with serious adverse effects such as increased risk of opportunistic infections and the development of neoplasms. This challenge underscores the urgent need for novel strategies to prevent graft rejection while abrogating toxicity-associated adverse events. Areas covered We review recent advances in immunoengineering strategies for localized immunomodulation that aim to support allograft function and provide immune tolerance in a safe and effective manner. Expert opinion Immunoengineering strategies are tailored approaches for achieving immunomodulation of the transplant microenvironment. Biomaterials can be adapted for localized and controlled release of immunomodulatory agents, decreasing the effective dose threshold and frequency of administration. The future of transplant rejection management lies in the shift from systemic to local immunomodulation with suppression of effector and activation of regulatory T cells, to promote immune tolerance.

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