Advances in Subclinical and Clinical Trials and Immunosuppressive Therapies in Xenotransplantation

Organ transplantation remains the foremost effective intervention for end-stage organ failure. Nevertheless, the scarcity of donors has resulted in prolonged waiting times for countless patients globally. The advent of xenografts presents a promising solution to the organ shortage crisis. Although the utilization of xenografts has a long history, it is only in recent years that breakthroughs in genetically modified pigs have rendered successful xenotransplantation a feasible option. In the past 4 years, numerous subclinical and clinical trials have involved xenotransplantation from genetically modified pigs to humans. However, the outcomes have been disappointing, necessitating a reassessment of basic and preclinical research to address the emerging challenges. Furthermore, immunosuppressive therapies remain essential in xenotransplantation. The range of immunosuppressive agents, encompassing traditional immunosuppressants and monoclonal antibodies such as anti-CD154/CD40 monoclonal antibodies, exhibits considerable diversity. However, the most effective drug combination for achieving optimal efficacy remains elusive. This review will offer a succinct overview of the results from recent clinical and subclinical xenotransplantation trials. Moreover, it will highlight recent advancements in immunosuppressive strategies and discuss potential future research directions in this field.