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<p style="margin: 0in; font-family: Aptos, sans-serif; font-size: 12pt;"><span style="font-family: Arial, sans-serif; font-size: 13.5pt; color: black;"><img alt="Dissertation Defense Announcement at the Cullen College of Engineering" id="x_Picture_x0020_4" width="600" height="170" style="width: 6.25in; height: 1.7812in; margin-top: 0px; margin-bottom: 0px;" data-outlook-trace="F:1|T:1" src="cid:image001.png@01DA9631.FC5F0320"></span></p>
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<span style="font-size: 18pt; color: rgb(200, 16, 46);"><b>Manufacturing of Adoptive Induced Regulatory T Cell Therapy for Autoimmune Diseases</b></span></p>
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<span style="font-size: 13.5pt; color: black;"><b>Kumar Abhishek</b></span></p>
<p align="center" style="line-height: 15pt;"><span style="font-size: 10.5pt; color: black;">April 25, 2024; 03:00 PM - 05:00 PM (CST)<br>
Location: SERC 2028<br>
<u><a href="https://urldefense.com/v3/__https://uh-edu-cougarnet.zoom.us/j/89793899572?pwd=Y0JkTnNlSXRiSzlmUFgzeG9BYmo0UT09__;!!LkSTlj0I!FvnmIJ9GJYS34PCUXH6aE_vaUEarVlEl0Nb47Q-2ADmwlY5VKQPZlnn--9ins-ITaUMsrBejyBaZA3KPGxrfizoPbPk$" title="https://uh-edu-cougarnet.zoom.us/j/89793899572?pwd=Y0JkTnNlSXRiSzlmUFgzeG9BYmo0UT09" data-auth="NotApplicable" style="color: black; margin-top: 0px; margin-bottom: 0px;" id="OWA53359d04-4fb8-92c7-b27f-3f38083bdeae" class="OWAAutoLink" data-loopstyle="linkonly">Zoom:
https://uh-edu-cougarnet.zoom.us/j/91275322202?pwd=akhuU1hncVFsZWFYUVRWTEZXOTZZQT09</a></u></span></p>
<p align="center" style="line-height: 15pt; margin-bottom: 3.75pt;"><span style="font-size: 10.5pt; color: black;"><b>Committee Chair:</b><br>
Sergey S. Shevkoplyas, Ph.D.</span></p>
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<span style="font-size: 10.5pt; color: black;"><b>Committee Members:</b><br>
Chandra Mohan, Ph.D. | Tianfu Wu, Ph.D. | Renita Horton, Ph.D. | Fong W. Lam, MD</span></p>
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<span style="font-family: Arial, sans-serif; color: rgb(200, 16, 46);"><b>Abstract</b></span></p>
<p style="text-align: justify; text-indent: 0.5in; margin-bottom: 6pt;"><span style="color: black;">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.</span></p>
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<span style="color: black;">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.</span></p>
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<span style="color: black;">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.</span></p>
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<p style="margin: 0in; font-family: Aptos, sans-serif; font-size: 12pt;"><span style="font-family: Arial, sans-serif; font-size: 13.5pt; color: black;"><img alt="Engineered For What's Next" id="x_Picture_x0020_5" width="600" height="81" style="width: 6.25in; height: 0.8541in; margin-top: 0px; margin-bottom: 0px;" data-outlook-trace="F:1|T:1" src="cid:image002.png@01DA9631.FC5F0320"></span></p>
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