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Advancing liver cancer treatment with dual-targeting CAR-T therapy.

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Title: Advancing liver cancer treatment with dual-targeting CAR-T therapy.
Authors: Yang, Ze1,2,3 (AUTHOR), Cheng, Chao4 (AUTHOR), Li, Zhongliang3,5 (AUTHOR), Wang, Huajing4 (AUTHOR), Zhang, Mengmei2 (AUTHOR), Xie, Ermin4 (AUTHOR), He, Xu1 (AUTHOR), Liu, Bing1 (AUTHOR), Sun, Hongwei3 (AUTHOR), Wang, Jiantao4 (AUTHOR), Li, Xiaopei4 (AUTHOR), Liu, Dingjie3 (AUTHOR), Lin, Xiaowen3 (AUTHOR), Li, Xianyang4 (AUTHOR), Jiang, Ping1 (AUTHOR), Lu, Ligong1,3 (AUTHOR), He, Xiaowen4 (AUTHOR) peterhe@oricell.com, Zhan, Meixiao1,3 (AUTHOR) zhanmeixiao1987@126.com, He, Ke6 (AUTHOR) hiker00006@126.com, Zhao, Wei1,3 (AUTHOR) zhaoweismu@foxmail.com
Source: Journal of Nanobiotechnology. 6/24/2025, Vol. 23 Issue 1, p1-15. 15p.
Subjects: Cell surface antigens, T cell receptors, Medical sciences, HLA histocompatibility antigens, Liver cancer, T cells
Abstract: Chimeric antigen receptor (CAR)-T cell therapy targeting glypican-3 (GPC3) has shown promise in the treatment of hepatocellular carcinoma (HCC). However, the efficacy of CAR-T cells that focus solely on cell surface tumor-associated antigens is often limited. To overcome this challenge, we developed a dual-targeting CAR-T cell strategy. The intracellular alpha-fetoprotein (AFP) antigen, a well-established biomarker of liver cancer, presents the immunogenic Human Leukocyte Antigen (HLA)-A*02:01-restricted epitope 158–166. Consequently, we engineered a T cell receptor (TCR) mimic antibody with high specificity and affinity, providing a promising therapeutic avenue to target this critical antigen. To enhance treatment outcomes for liver cancer, we further modified previously developed GPC3 CAR-T cells, which demonstrated robust anti-tumor efficacy against GPC3-high tumor cells, to secrete an optimized bispecific T cell engager (BiTE) targeting the presented AFP antigen. This dual-targeting strategy significantly improved CAR-T cell proliferation and persistence, as well as enhancing cytokine expression and anti-tumor activity against HCC cells, particularly those exhibiting low GPC3 and AFP expression, both in vitro and in vivo. Our findings highlight the potential of this innovative approach to offer more effective treatment options for patients with liver cancer. Graphical sbstract: [ABSTRACT FROM AUTHOR]
Copyright of Journal of Nanobiotechnology is the property of BioMed Central and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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DbLabel: Engineering Source
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PubType: Academic Journal
PubTypeId: academicJournal
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  Data: Advancing liver cancer treatment with dual-targeting CAR-T therapy.
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  Data: <searchLink fieldCode="AR" term="%22Yang%2C+Ze%22">Yang, Ze</searchLink><relatesTo>1,2,3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Cheng%2C+Chao%22">Cheng, Chao</searchLink><relatesTo>4</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Li%2C+Zhongliang%22">Li, Zhongliang</searchLink><relatesTo>3,5</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wang%2C+Huajing%22">Wang, Huajing</searchLink><relatesTo>4</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhang%2C+Mengmei%22">Zhang, Mengmei</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Xie%2C+Ermin%22">Xie, Ermin</searchLink><relatesTo>4</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22He%2C+Xu%22">He, Xu</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Liu%2C+Bing%22">Liu, Bing</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Sun%2C+Hongwei%22">Sun, Hongwei</searchLink><relatesTo>3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wang%2C+Jiantao%22">Wang, Jiantao</searchLink><relatesTo>4</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Li%2C+Xiaopei%22">Li, Xiaopei</searchLink><relatesTo>4</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Liu%2C+Dingjie%22">Liu, Dingjie</searchLink><relatesTo>3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Lin%2C+Xiaowen%22">Lin, Xiaowen</searchLink><relatesTo>3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Li%2C+Xianyang%22">Li, Xianyang</searchLink><relatesTo>4</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Jiang%2C+Ping%22">Jiang, Ping</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Lu%2C+Ligong%22">Lu, Ligong</searchLink><relatesTo>1,3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22He%2C+Xiaowen%22">He, Xiaowen</searchLink><relatesTo>4</relatesTo> (AUTHOR)<i> peterhe@oricell.com</i><br /><searchLink fieldCode="AR" term="%22Zhan%2C+Meixiao%22">Zhan, Meixiao</searchLink><relatesTo>1,3</relatesTo> (AUTHOR)<i> zhanmeixiao1987@126.com</i><br /><searchLink fieldCode="AR" term="%22He%2C+Ke%22">He, Ke</searchLink><relatesTo>6</relatesTo> (AUTHOR)<i> hiker00006@126.com</i><br /><searchLink fieldCode="AR" term="%22Zhao%2C+Wei%22">Zhao, Wei</searchLink><relatesTo>1,3</relatesTo> (AUTHOR)<i> zhaoweismu@foxmail.com</i>
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  Data: <searchLink fieldCode="JN" term="%22Journal+of+Nanobiotechnology%22">Journal of Nanobiotechnology</searchLink>. 6/24/2025, Vol. 23 Issue 1, p1-15. 15p.
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  Data: <searchLink fieldCode="DE" term="%22Cell+surface+antigens%22">Cell surface antigens</searchLink><br /><searchLink fieldCode="DE" term="%22T+cell+receptors%22">T cell receptors</searchLink><br /><searchLink fieldCode="DE" term="%22Medical+sciences%22">Medical sciences</searchLink><br /><searchLink fieldCode="DE" term="%22HLA+histocompatibility+antigens%22">HLA histocompatibility antigens</searchLink><br /><searchLink fieldCode="DE" term="%22Liver+cancer%22">Liver cancer</searchLink><br /><searchLink fieldCode="DE" term="%22T+cells%22">T cells</searchLink>
– Name: Abstract
  Label: Abstract
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  Data: Chimeric antigen receptor (CAR)-T cell therapy targeting glypican-3 (GPC3) has shown promise in the treatment of hepatocellular carcinoma (HCC). However, the efficacy of CAR-T cells that focus solely on cell surface tumor-associated antigens is often limited. To overcome this challenge, we developed a dual-targeting CAR-T cell strategy. The intracellular alpha-fetoprotein (AFP) antigen, a well-established biomarker of liver cancer, presents the immunogenic Human Leukocyte Antigen (HLA)-A*02:01-restricted epitope 158–166. Consequently, we engineered a T cell receptor (TCR) mimic antibody with high specificity and affinity, providing a promising therapeutic avenue to target this critical antigen. To enhance treatment outcomes for liver cancer, we further modified previously developed GPC3 CAR-T cells, which demonstrated robust anti-tumor efficacy against GPC3-high tumor cells, to secrete an optimized bispecific T cell engager (BiTE) targeting the presented AFP antigen. This dual-targeting strategy significantly improved CAR-T cell proliferation and persistence, as well as enhancing cytokine expression and anti-tumor activity against HCC cells, particularly those exhibiting low GPC3 and AFP expression, both in vitro and in vivo. Our findings highlight the potential of this innovative approach to offer more effective treatment options for patients with liver cancer. Graphical sbstract: [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Journal of Nanobiotechnology is the property of BioMed Central and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1186/s12951-025-03512-w
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        Text: English
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      – SubjectFull: HLA histocompatibility antigens
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      – SubjectFull: Liver cancer
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              Text: 6/24/2025
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