title: Reshape of CAR-T cells by overexpression of TCF-1
creator: Yao, Hao
subject: ddc-570
subject: 570 Life sciences
subject: ddc-610
subject: 610 Medical sciences Medicine
description: Despite the remarkable success of CAR-T cell therapy in leukemia and lymphoma patients, lack of CAR-T cell persistence remains a significant clinical problem. In particular, CAR-T cells often exhibit a deficiency in TCF-1 expression, rendering cells susceptible to TCF-1-associated pathways and consequently to short survival in the host. Therefore, it is intriguing to modulate TCF-1 expression in CAR-T cells to address the challenge of CAR-T cell persistence and further improve therapeutic outcomes.  In this study, third generation CAR vectors were used, and a double transduction system was established. The effect of TCF-1 overexpression in CAR-T cells was comprehensively explored regarding various aspects. Given the phenotype and functionality of CAR-T cells after transduction, two different CAR models (CD19.CAR vector and CD33.CAR vector) were settled in the study to generalize the effect of overexpression of TCF-1. We found that (1) the overexpression of TCF-1 can enrich the naïve and stem cell-like CAR-T cells exhibiting a better killing efficacy; (2) the cytokine profile of CAR-T cells were switched from proinflammatory or killing related to inactive through overexpression of TCF-1; (3) the apoptotic status of CAR- T cells could be modulated by TCF-1 overexpression, thus resulting in a better long- term functionality in terms of repetitive tumor killing and reduced multiple inhibitory receptors.  In summary, overexpression of TCF-1 in CAR-T cells could reduce apoptosis, occurrence of CRS and improve their persistence, resulting in enhanced antitumor efficacy of CAR-T cells. Thus, overexpression of TCF-1 might improve CAR-T cell persistence in vivo and enhance the effect of CAR-T cell therapy in patients with relapsed/refractory hematologic malignancies.
date: 2025
type: Dissertation
type: info:eu-repo/semantics/doctoralThesis
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserver/36449/1/Yao_Hao_1992_12_28_Reshape%20of%20CAR_T%20cells%20by%20overexpression%20of%20TCF_1.pdf
identifier: DOI:10.11588/heidok.00036449
identifier: urn:nbn:de:bsz:16-heidok-364494
identifier:   Yao, Hao  (2025) Reshape of CAR-T cells by overexpression of TCF-1.  [Dissertation]     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/36449/
rights: info:eu-repo/semantics/openAccess
rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html
language: eng