Periodic Reporting for period 3 - VANGUARD (New Generation Cell Therapy: Bioartificial Pancreas to Cure Type 1 Diabetes)
Período documentado: 2022-07-01 hasta 2023-12-31
Type I diabetes is a global epidemic associated with a shortage of insulin-producing beta cells in the pancreas and is usually diagnosed in children and young adults. The current primary treatment for T1DM is exogenous insulin therapy, requiring multiple daily injections to control glucose levels. Poor glucose control leads to diabetes complications such as disease of the kidney, eyes and heart. During the last decades, important signs of progress have been made in clinical islet transplantation. However, islet transplantation relies on organ donors and requires lifelong immunosuppression to avoid the rejection of the transplanted islets. The process is also associated with a number of other complications and is currently only offered to a limited number of patients with severe forms of the disease.
VANGUARD aims to develop a cure for type 1 diabetes and thus make cell therapy a real and effective treatment available to a larger group of patients. The overarching objective of VANGUARD is to generate a novel breakthrough immune-protected bio-artificial pancreas that can be transplanted into non-immuno-suppressed patients. To achieve this VANGUARD will combine advanced tissue engineering platforms for 3D organoid generation, hydrogel design and bio-artificial organ assembly.
The project has the potential to drastically improve the success rate of clinical beta-cell replacement therapies, with exceptional advantages in terms of efficacy and patient safety. A bioartificial pancreas offers a breakthrough in the field of regenerative medicine and opens new horizons toward unlimited cell-based treatments for type 1 diabetes, thus overcoming the constraint of donor organ shortage.
VANGUARD aims to develop a cure for type 1 diabetes and thus make cell therapy a real and effective treatment available to a larger group of patients. The overarching objective of VANGUARD is to generate a novel breakthrough immune-protected bio-artificial pancreas that can be transplanted into non-immuno-suppressed patients. To achieve this VANGUARD will combine advanced tissue engineering platforms for 3D organoid generation, hydrogel design and bio-artificial organ assembly.
The project has the potential to drastically improve the success rate of clinical beta-cell replacement therapies, with exceptional advantages in terms of efficacy and patient safety. A bioartificial pancreas offers a breakthrough in the field of regenerative medicine and opens new horizons toward unlimited cell-based treatments for type 1 diabetes, thus overcoming the constraint of donor organ shortage.
By the end of the third reporting period, the consortium has refined the organoid generation protocol, leading to organoids that show improved glucose-stimulated insulin secretion and enhanced vascularization post-transplantation in immune-deficient mice. Hydrogels developed and distributed within the consortium have proven to support cell function and viability both in vitro and in vivo. The bioartificial pancreas assembly protocols have been optimized, ensuring component functionality, biocompatibility, and non-toxicity. The immunomodulatory cells have been successfully established. The consortium is currently exploring further gene modifications to enhance their immunomodulatory capabilities. The progress continues with ethical, legal, and psychosocial research. The consortium has made strides in scaling up spheroid production, focusing on standardization and compliance with GMP protocols.
For the past 20 years, and despite all its limitations, the current state of the art in clinical cell therapy for type 1 diabetes has consisted of islet of Langerhans transplantation (i.e. transplantation of the unmodified insulin-secreting mini-organs enzymatically extracted from a donor pancreas). A few clinical attempts at transplanting ATMP have reached phase 1 level, but have failed to show any clinically relevant effect.
Ambitious projects have even started by combining a macroencapsulation device strategy with stem cell-derived beta cells or xenogeneic islets, without first going through an allogeneic stage. In contrast, VANGUARD will use a stepwise strategy, moving from allogeneic islet cell organoids to a more complex, but still allogeneic, bioartificial pancreas, constructed by “encapsulating” organoids into a biological scaffold.
The primary ambition of the VANGUARD consortium is to deliver a game-changing ATMP in the treatment of type 1 diabetes. The major deliverable of the project will represent a major breakthrough compared to islet of Langerhans transplantation, the only cell therapy for diabetes current in clinical practice. Breakthrough achievements are represented by increased potency/efficiency that will allow single-donor transplantation, immune protection that will dispense with the use of chronic systemic immunosuppression, and graft retrievability. Furthermore, VANGUARD strategy will dramatically reduce the long-term financial burden of the diabetic disease as well as the human consequences in terms of quality of life, permitting the large-scale treatment of diabetes at non-complicated stages through functional transplantation without the drawbacks of full immunosuppression.
Ambitious projects have even started by combining a macroencapsulation device strategy with stem cell-derived beta cells or xenogeneic islets, without first going through an allogeneic stage. In contrast, VANGUARD will use a stepwise strategy, moving from allogeneic islet cell organoids to a more complex, but still allogeneic, bioartificial pancreas, constructed by “encapsulating” organoids into a biological scaffold.
The primary ambition of the VANGUARD consortium is to deliver a game-changing ATMP in the treatment of type 1 diabetes. The major deliverable of the project will represent a major breakthrough compared to islet of Langerhans transplantation, the only cell therapy for diabetes current in clinical practice. Breakthrough achievements are represented by increased potency/efficiency that will allow single-donor transplantation, immune protection that will dispense with the use of chronic systemic immunosuppression, and graft retrievability. Furthermore, VANGUARD strategy will dramatically reduce the long-term financial burden of the diabetic disease as well as the human consequences in terms of quality of life, permitting the large-scale treatment of diabetes at non-complicated stages through functional transplantation without the drawbacks of full immunosuppression.