Emerging local immunomodulatory strategies to circumvent systemic immunosuppression in cell transplantation

Expert Opin Drug Deliv. 2022 May;19(5):595-610. doi: 10.1080/17425247.2022.2076834. Epub 2022 May 29.

Abstract

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.

Keywords: Local immunosuppression; cell therapy; immunomodulation; long-acting drug delivery.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Transplantation
  • Graft Rejection / prevention & control
  • Immune Tolerance*
  • Immunomodulation
  • Immunosuppression Therapy*
  • Immunosuppressive Agents / therapeutic use

Substances

  • Immunosuppressive Agents