Can a novel ‘immunotoxin’ prevent transplant rejection in heart failure?

Prolonging cardiac allograft survival by targeting the indirect antigen presentation pathway with an immunotoxin

Although heart transplants are a highly effective option for the treatment of people with heart failure, organ rejection remains a significant hurdle. This is especially the case with chronic rejection, which can occur several months or years after a transplant. There are three ‘pathways’ that the recipient’s immune system uses to recognise the donor heart as foreign: direct, indirect and semi-direct. The indirect pathway is thought to be important in chronic rejection and this project aims to test whether a potential ‘immunotoxin’ treatment can prevent it. Dr Wong’s team has previously worked on an immunotoxin that aimed to kill the immune cells that are part of the direct pathway. This successfully prolonged the survival of heart transplants in mice. In this new project, they will design a new immunotoxin that will block the indirect pathway in mice that have been engineered to have an immune system similar to humans. The goal of this research is to use these immunotoxins to shut down all the pathways that the immune system uses to reject a donor heart. Because the immunotoxins have been designed to affect cells with human-like proteins, it could quickly be adapted for use in people with heart failure. If successful, the immunotoxins could help prevent transplant rejection without leaving the recipient prone to infections and other side effects that are associated with existing immunosuppressive treatments.