Objective
Our primary objective is to develop and validate new cellular therapies that will be used to treat individuals with type 1 diabetes (T1D). This proposal will bring together scientists from the Diabetes Center of Excellence at the UMass Chan Medical School and Abata Therapeutics to work collaboratively to develop new therapies. The collaborating scientists have expertise with cellular engineering, T1D disease mechanisms, and novel humanized mouse models for the study of human disease. The complementary skill sets will provide a strong foundation to complete the proposed experiments in a timely manner. The ultimate goal is to provide a safe, effective and accessible therapy for T1D.
Background Rationale
While significant progress has been made in the disease management of T1D, a true cure is still lacking. Cellular therapies are emerging as potential candidates for both the replacement of functional pancreatic β-cells in individuals with T1D and for suppression of the autoimmune response which destroys the β-cell. However, testing and validation of these cellular therapies is challenging given the lack of experimental models that fully recreate human T1D. The rationale for the proposed studies is to develop an innovative cellular therapy to suppress autoimmune disease and at the same time use cutting-edge humanized mouse models to validate these therapies. Our collaborative team has extensive experience with the development of cellular therapies and has pioneered the development of new humanized mouse models to study human disease.
Description of Project
The standard of care for individuals living with type 1 diabetes (T1D) is the lifelong use of injectable insulins. While significant technological advancements have been made for more effective insulin formulations, the delivery of insulin via pump systems and the use of continuous glucose meters, a permanent cure for the underlying disease has not been achieved. Cellular therapies are emerging as potential candidates for both the replacement of functional pancreatic β-cells in individuals with T1D and for suppression of the autoimmune response which destroys the β-cell. However, testing and validation of these cellular therapies is challenging given the lack of experimental models that fully recreate human T1D. Ideally, immune-targeting therapeutics will suppress specifically the autoimmune response in individuals with T1D but will not impact the overall ability of the immune system to control pathogens and malignancies. Our proposal will develop cellular therapies that directly target the immune response in the pancreas of individuals with T1D and will not impact function of the overall immune system. The rationale for the proposed studies is to develop an innovative cellular therapy to suppress autoimmune disease and at the same time use cutting-edge humanized mouse models to validate these therapies. This proposal will bring together scientists from the Diabetes Center of Excellence at the UMass Chan Medical School and at Abata Therapeutics to work collaboratively to develop new cellular therapies targeting autoimmunity. The collaborating scientists have expertise with cellular engineering, T1D disease mechanisms, and novel humanized mouse models for the study of human disease. The complementary skill sets will provide a strong foundation to complete the proposed experiments in a timely manner. We anticipate that at the end of the funding period that we will have developed a panel of cellular therapeutic agents and created a groundbreaking humanized mouse model to screen and validate human-specific therapeutics. A primary endpoint will be to translate developed cellular therapies into a clinical setting for the treatment of T1D. We will also make the new humanized models available to other investigators to test T1D-focused therapeutics. If successful, the platforms may be applicable for the development and testing of cellular therapies for additional autoimmune disorders. Our ultimate goal is to provide a safe, effective and accessible therapy for T1D.
Anticipated Outcome
We anticipate that at the end of the funding period that we will have developed a panel of cellular therapeutic agents and created a groundbreaking humanized mouse model to screen and validate human-specific therapeutics. A primary endpoint will be to translate developed cellular therapies into a clinical setting for the treatment of T1D. We will also make the new humanized models available to other investigators to test T1D-focused therapeutics. If successful, the platforms may be applicable for the development and testing of cellular therapies for additional autoimmune disorders.
Relevance to T1D
Despite decades of groundbreaking research into the disease mechanisms of T1D, a cure has remained elusive. Ideally, therapeutics will suppress specifically the autoimmune response in individuals with T1D but will not impact the overall ability of the immune system to control pathogens and malignancies. Our proposal will develop cellular therapies that directly target the immune response in the pancreas of individuals with T1D and will not impact function of the overall immune system.