[CCoE Notice] Cullen College Dissertation Announcement

[Hutchinson, Inez A]

[Dissertation Defense Announcement at the Cullen College of Engineering]

Manufacturing of Adoptive Induced Regulatory T Cell Therapy for Autoimmune Diseases

Kumar Abhishek

April 25, 2024; 03:00 PM - 05:00 PM (CST)
Location: SERC 2028
Zoom: https://urldefense.com/v3/__https://uh-edu-cougarnet.zoom.us/j/91275322202?pwd=akhuU1hncVFsZWFYUVRWTEZXOTZZQT09__;!!LkSTlj0I!FvnmIJ9GJYS34PCUXH6aE_vaUEarVlEl0Nb47Q-2ADmwlY5VKQPZlnn--9ins-ITaUMsrBejyBaZA3KPGxrfeZnNSdQ$ <https://urldefense.com/v3/__https://uh-edu-cougarnet.zoom.us/j/89793899572?pwd=Y0JkTnNlSXRiSzlmUFgzeG9BYmo0UT09__;!!LkSTlj0I!FvnmIJ9GJYS34PCUXH6aE_vaUEarVlEl0Nb47Q-2ADmwlY5VKQPZlnn--9ins-ITaUMsrBejyBaZA3KPGxrfizoPbPk$ >

Committee Chair:
Sergey S. Shevkoplyas, Ph.D.

Committee Members:
Chandra Mohan, Ph.D. | Tianfu Wu, Ph.D. | Renita Horton, Ph.D. | Fong W. Lam, MD

Abstract

Regulatory T cells (Tregs) are a specialized subset of CD4+ T cells that play a crucial role in maintaining self-tolerance by suppressing immune responses against self-antigens. Dysfunction or depletion of Tregs can lead to the breakdown of self-tolerance, resulting in autoimmune diseases. Adoptive Treg cell therapy is a promising approach to restore self-tolerance and alleviate autoimmune symptoms by infusing ex vivo expanded autologous Tregs. Despite the demonstrated efficacy and safety of Treg therapy in preclinical and clinical studies, the lack of specific Treg markers and their low prevalence in peripheral blood (< 5% of CD4+ T cells) pose significant challenges for manufacturing Tregs in sufficient quantities for clinical applications.

This dissertation aims to develop an efficient process for manufacturing Tregs that can overcome the current manufacturing challenges and potentially drive Treg therapy toward commercialization. First, a systematic review of published data from Treg therapy clinical trials was conducted to understand the limitations of the existing Tregs isolation and expansion protocols. The review highlighted the suboptimal isolation approaches, which require processing large volumes of blood (up to 500 mL) to obtain adequate number of Tregs for ex vivo expansion, often taking up to 5 weeks. To address these challenges, we developed a novel rosette-enabled size-based separation (RESIZE) method to isolate immune cells from blood with high yield and purity for cell therapy applications. Additionally, instead of directly isolating low prevalence natural Tregs (nTregs) from the blood, we pursued an alternative approach of isolating the more prevalent CD4+ T cells to induce Tregs (iTregs) in cell culture. We successfully demonstrated the efficient generation of clinically relevant numbers of iTregs using a small volume of blood (8 mL) in 2 weeks, which can potentially overcome the limitations of current Treg manufacturing protocols.

The advancements made in this dissertation, including the development of the RESIZE method and the successful generation of iTregs, represent significant progress towards overcoming the key challenges in Treg therapy manufacturing. These innovative approaches could contribute to the further development and potential commercialization of Treg-based immunotherapies for autoimmune diseases.

[Engineered For What's Next]




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