PHOENIX: Nanomedicine for Organ Transplantation Tolerance
The Future of Organ Transplantation: Science, Innovation, and Hope
Every day, thousands of patients across the globe await the life-saving gift of an organ transplant. For many, it is a race against the clock, as the demand for healthy organs far outstrips the supply. However, thanks to remarkable advancements in medical research, organ transplantation is undergoing a revolutionary transformation—one that promises to increase availability, enhance success rates, and change lives.
A History of Life-Saving Breakthroughs
Organ transplantation has come a long way since the first successful kidney transplant in 1954. Since then, surgeons have mastered procedures for transplanting kidneys, hearts, lungs, and livers. Today, with improved surgical techniques and sophisticated immunosuppressive medications, the survival rates of people with transplanted organs have never been higher.
Despite these successes, challenges remain, and researchers work tirelessly to overcome them
Transplantation success rates have seen significant improvements in recent years; however, the necessity for lifelong immunosuppression poses challenges. This ongoing treatment broadly dampens the immune system of organ recipients, which can lead to increased vulnerability to infections and cancer, as well as heightened risks for cardiovascular and metabolic diseases. For instance, in people with kidney transplants, the likelihood of developing cancer rises from 4-5% after five years to 10% after ten years and exceeds 25% after two decades. This situation places physicians in a difficult position, as they must navigate the delicate balance between reducing immunosuppression to lower the risk of these complications while managing the potential for organ rejection and graft failure. There is a pressing need for new therapies that can promote graft tolerance, potentially reducing or even eliminating the need for lifelong immunosuppression. This is fundamentally the aim of the PHOENIX Project.
The PHOENIX Project
The PHOENIX Project aims to develop a novel nano-immunotherapy consisting of nanoparticles coated with a peptide complex coat designed to reprogram the anti-graft immune cells of the patient, converting them through various processes into regulatory cells that promote graft tolerance. This process aims to create a localised tolerant environment around the transplanted organ, or graft while preserving the overall systemic immunity of the person with the transplant. The research framework of PHOENIX is grounded in peer-reviewed studies1 that have demonstrated the reprogramming of immune cells to alleviate autoimmune diseases.2 The project partners are adapting this technology to reprogram graft-reactive T cells, which are known to attack transplanted organs, and validating these nano-medicines in pre-clinical models of kidney and liver transplantation, thereby establishing a robust foundation for future clinical trials.
PHOENIX is an EU-funded research project coordinated by Professor Giuseppe Remuzzi, MD, director of the Mario Negri Pharmacological Research Institute in Bergamo, Italy. Five partner institutions across four countries are building on a promising foundation to deliver a novel therapy that will have a transformative, positive effect on people with organ transplants and healthcare generally.
Partners in four countries
Italy: Istituto di Ricerche Farmacologiche Mario Negri IRCCS
Spain: Institut D’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
France: Central Hospitalier Universitaire de (CHU) Rennes and INRAE
Ireland: Pintail Limited
Main objectives
PHOENIX presents an innovative approach to nano-immunotherapy, utilising nanoparticles that are coated with specific peptides. These nano-therapies aim to reprogram the recipient’s anti-graft immune cells into regulatory cells that foster a tolerant environment for the transplanted organ while avoiding the systemic consequences associated with lifelong immunosuppression. Currently, these nano-therapies are in the preclinical validation stage, being tested in kidney and liver transplants to establish strong evidence for forthcoming clinical trials. The primary objective of the PHOENIX Project is to illustrate that these nano-therapies can initiate the formation of immunoregulatory cell networks within the graft environment and promote transplant tolerance, all without compromising the host’s immune responses to cancers, vaccines or infections.
“This next-generation immunotherapy has the potential to transform the lives of millions of people worldwide by minimizing the risks associated with organ transplantation,” comments Professor Giuseppe Remuzzi, MD, Director of the Mario Negri Institute.
Benefits
PHOENIX paves the way for successful organ transplants without the need for lifelong immunosuppression, offering significant advantages to millions of individuals, healthcare systems, and society in general. The innovative nano-therapies will alleviate the challenges faced by organ transplant recipients, minimising the necessity for additional transplants and shortening the waiting periods for new patients. This approach allows patients to steer clear of the negative consequences associated with long-term immunosuppression, leading to longer, higher-quality lives. Additionally, the impact of PHOENIX’s nano-therapies will be profound, easing the financial strain on healthcare systems.
To learn more about the PHOENIX Project, visit our website (www. phoenix.eu) and join us on X, @phoenix_nano, LinkedIn https:// www.linkedin.com/company/ phoenix-horizon-europe/ and Facebook.
Funded by the European Union. Views and opinions expressed are however those of the authors only and do not necessarily reflect those of the European Union or the European Health and Digital Executive Agency (HaDEA). Neither the European Union nor the granting authority can be held responsible for them.
References
- https://www.nature.com/articles/nature16962 , https:// www.nature.com/articles/nrrheum.2016.33
- https://clinicaltrials.gov/study/ NCT06798454
Written by Danielle Nicholson, Pintail Limited
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