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CCR10-Mediated Enhancement of T Cell Trafficking for Improved Tumor Immunotherapy

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Alternative Title
CCR10-Mediated Enhancement of T Cell Trafficking for Improved Tumor Immunotherapy
Abstract
The efficacy of adoptive T cell therapy is still not optimal for solid tumors, in part due to the insufficient T cell infiltration into the tumor site. An encouraging approach involves guiding T cells toward the tumor by utilizing tumor-specific chemokines, assuming that the corresponding chemokine receptor is present on the T cells. Analysis of RNA-seq data from TCGA and GTEx revealed high expression of the chemokine CCL28 in breast and lung cancer. However, the receptor for CCL28, CCR10 was found to have insufficient expression in human peripheral T cells, tumor-infiltrating T cells, and activated chimeric antigen receptors modified T cells (CAR-T). Hence, my goal was to utilize CCR10's potential to guide T cells to the tumor site and enhance the effectiveness of tumor immunotherapy. After expressing 1G4 in T cell receptor-engineered T cells (TCR-T), I employed cloning and lentivirus transduction to increase endogenous CCR10 expression. CCR10-1G4 dual expressing TCR-T exhibited comparable cellular cytotoxicity but demonstrated increased mobility in vitro. CCR10-1G4 dual expressing TCR-T injection to a xenograft tumor model exhibited enhanced in vivo trafficking and greater reduction of tumor burden in treated mice, compared to 1G4 TCR-T. This study not only elucidates the role of CCR10 in T-cell trafficking but also presents its potential for developing treatments targeting malignant tumors.
Author(s)
홍종무
Issued Date
2024
Awarded Date
2024-02
Type
Dissertation
URI
https://oak.ulsan.ac.kr/handle/2021.oak/13007
http://ulsan.dcollection.net/common/orgView/200000731212
Alternative Author(s)
Jong Moo Hong
Affiliation
울산대학교
Department
일반대학원 의과학과 의과학전공
Advisor
Hee Jin Lee
Degree
Master
Publisher
울산대학교 일반대학원 의과학과 의과학전공
Language
eng
Rights
울산대학교 논문은 저작권에 의해 보호받습니다.
Appears in Collections:
Medical Science > 1. Theses (Master)
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