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TCR 과 Co-stimulatory ICD 직접 연결 엔지니어링을 통한 TCR-T 기능 향상 가능성

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Alternative Title
Possibility of improving TCR-T function through engineering method of directly combining 1G4 TCR and T cell co-stimulatory molecule ICD
Abstract
This study proposes a novel approach to enhance the efficacy of adoptive T cell therapy (ACT), a form of immunotherapy for cancer treatment. Among ACT strategies, T cell receptor-engineered T (TCR-T) therapy can be applied to solid tumors by expressing TCRs on patient T cells to recognize tumor antigens and eradicate cancer cells. However, a significant challenge in ACT is the limited activation of T cells within the tumor microenvironment, leading to suppressed immune responses and reduced effectiveness. Therefore, we investigated methods to improve T cell function using the TCR-T system. Similar to techniques used in Chimeric Antigen Receptor T (CAR-T) therapies, we designed an engineering approach to directly link the intracellular domain (ICD) of co-stimulatory molecules to the TCR constant region. We aimed to assess the impact of this modification on T cell activation and anti-tumor effects. Using lentivirus-mediated gene delivery, we confirmed stable TCR expression levels in both cell lines and human primary cells. However, contrary to expectations, this modification did not enhance anti-tumor effects compared to conventional TCR in human primary cells; in some cases, these effects were diminished. Nevertheless, the engineering approach of directly linking the ICD of co-stimulatory molecules statistically significantly increased T cell activation levels compared to conventional TCR. These results resemble enhanced activation responses observed in CAR-T research, demonstrating the feasibility of a second-generation TCR-T system that successfully integrates signals 1 and 2. Therefore, the direct coupling of co-stimulatory molecule ICD to TCR via engineering provides a new strategy in TCR-T engineering to enhance ACT functionality, suggesting potential improvements in the field of immune oncology therapy
Author(s)
김종혁
Issued Date
2024
Awarded Date
2024-08
Type
Dissertation
Keyword
TCR Engineering
URI
https://oak.ulsan.ac.kr/handle/2021.oak/13295
http://ulsan.dcollection.net/common/orgView/200000810406
Alternative Author(s)
KIM JONGHYEOK
Affiliation
울산대학교
Department
일반대학원 의과학과 의과학전공
Advisor
공경엽
Degree
Master
Publisher
울산대학교 일반대학원 의과학과 의과학전공
Language
kor
Rights
울산대학교 논문은 저작권에 의해 보호받습니다.
Appears in Collections:
Medical Science > 1. Theses (Master)
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