Related Experiment Video
Updated: Jan 4, 2026
A Nonviral Approach to Generate Transient Chimeric Antigen Receptor T Cells Using mRNA for Cancer Immunotherapy
Published on: February 21, 2025
Doxycycline Inducible Chimeric Antigen Receptor T Cells Targeting CD147 for Hepatocellular Carcinoma Therapy
Ren-Yu Zhang1, Ding Wei1, Ze-Kun Liu1
1Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, China.
Abstract:
Chimeric antigen receptor T cell (CAR-T) therapy to hematological malignancies has demonstrated tremendous clinical outcomes. However, the therapeutic efficacy of CAR-T cells in solid tumors remains limited due to the scarcity of tumor-specific antigen targets and the poor infiltration of CAR-T cells into tumor tissue. In this study, we developed a novel inducible CAR-T cell system which targets CD147, a tumor-associated antigen for hepatocellular carcinoma (HCC). To minimize potential toxicities of CAR-T cell therapy, the Tet-On 3G system was introduced to induce CD147CAR expression in the right place at the right time. Specifically, Tet-CD147CAR lentiviral vector (LV-Tet-CD147CAR) was constructed, which comprised CD147CAR controlled by the Tet-On system. Tet-CD147CART cells were successfully generated from activated T cells by infection with LV-Tet-CD147CAR. Proliferation, cytotoxicity, and cytokine secretion of Tet-CD147CART cells were significantly increased against CD147-positive cancer cells in the presence of doxycycline (Dox) compared to Tet-CD147CART cells in the absence of Dox and PBMCs. Consistently, in vivo studies indicated that the tumor growth in nude mice was significantly inhibited by (Dox+) Tet-CD147CART cells through multiple intratumoral administration. Taken together, our results indicated that the expression and activity of CD147CAR were controlled by Dox both in vitro and in vivo, which facilitated decreased toxicity and adverse effects to CAR-T cell therapy. Moreover, this study provides viable evidence in support of the potential benefits and translation of this strategy of CAR-T cells targeting CD147 for the treatment of patients with HCC.
Insights
This study introduces an inducible CAR-T cell therapy targeting CD147 for liver cancer. Doxycycline controlled the therapy
Area of Science:
- Immunotherapy
- Oncology
- Biotechnology
Background:
- CAR-T cell therapy shows success in blood cancers but faces challenges in solid tumors due to target scarcity and poor infiltration.
- Hepatocellular carcinoma (HCC) presents limited tumor-specific targets for effective CAR-T cell therapy.
- Minimizing CAR-T cell therapy toxicities is crucial for broader clinical application.
Purpose of the Study:
- To develop a novel inducible CAR-T cell system targeting CD147, a hepatocellular carcinoma (HCC)-associated antigen.
- To control CD147CAR expression and activity using the Tet-On 3G system to enhance therapeutic safety and efficacy.
- To evaluate the in vitro and in vivo performance of the Tet-On inducible CD147CAR-T cells.
Main Methods:
- Construction of a Tet-On inducible CD147CAR lentiviral vector (LV-Tet-CD147CAR).
- Generation of Tet-CD147CAR-T cells from activated T cells via lentiviral transduction.
- Assessment of Tet-CD147CAR-T cell proliferation, cytotoxicity, and cytokine secretion in vitro with and without doxycycline (Dox).
- Evaluation of in vivo anti-tumor efficacy in a nude mouse model of HCC with Dox-induced CAR-T cell administration.
Main Results:
- Tet-CD147CAR-T cells were successfully generated and demonstrated enhanced proliferation, cytotoxicity, and cytokine secretion against CD147-positive HCC cells in the presence of Dox.
- In vivo studies showed significant inhibition of tumor growth in nude mice treated with Dox-induced Tet-CD147CAR-T cells.
- Doxycycline effectively controlled the expression and activity of CD147CAR in vitro and in vivo, suggesting reduced potential toxicities.
Conclusions:
- The Tet-On inducible system successfully controlled CD147CAR-T cell activity, demonstrating potential for safer and more effective CAR-T cell therapy in HCC.
- This inducible CAR-T cell strategy targeting CD147 offers a promising therapeutic approach for hepatocellular carcinoma.
- The findings support the translational potential of Dox-controlled CD147CAR-T cells for HCC treatment, addressing key challenges in solid tumor immunotherapy.
More Related Videos
06:38An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
Published on: September 12, 2019
11:08Advances in Human Induced Pluripotent Stem Cell-Derived Chimeric Antigen Receptor-Expressing Natural Killer Cells
Published on: February 14, 2025
