The past, present, and future of costimulation blockade in organ transplantation

Curr Opin Organ Transplant. 2019 Aug;24(4):391-401. doi: 10.1097/MOT.0000000000000656.

Abstract

Purpose of review: Manipulating costimulatory signals has been shown to alter T cell responses and prolong graft survival in solid organ transplantation. Our understanding of and ability to target various costimulation pathways continues to evolve.

Recent findings: Since the approval of belatacept in kidney transplantation, many additional biologics have been developed targeting clinically relevant costimulation signaling axes including CD40-CD40L, inducible costimulator-inducible costimulator ligand (ICOS-ICOSL), and OX40-OX40L. Currently, the effects of costimulation blockade on posttransplant humoral responses, tolerance induction, and xenotransplantation are under active investigation. Here, we will discuss these pathways as well as preclinical and clinical outcomes of biologics targeting these pathways in organ transplantation.

Summary: Targeting costimultion is a promising approach for not only controlling T cell but also B cell responses. Consequently, costimulation blockade shows considerable potential for improving outcomes in antibody-mediated rejection and xenotransplantation.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Abatacept / pharmacology
  • Abatacept / therapeutic use*
  • Animals
  • Graft Rejection / physiopathology*
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Transplantation / methods*
  • Organ Transplantation / methods*
  • Swine
  • Transplantation, Heterologous

Substances

  • Immunosuppressive Agents
  • Abatacept