GPC3-CAR-T Cells for Immunotherapy of Cancer With GPC3 Expression
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|ClinicalTrials.gov Identifier: NCT03198546|
Recruitment Status : Recruiting
First Posted : June 26, 2017
Last Update Posted : December 1, 2020
|Condition or disease||Intervention/treatment||Phase|
|Hepatocellular Carcinoma Immunotherapy CAR GPC3 Gene Inactivation T Cell Squamous Cell Lung Cancer||Biological: GPC3 and/or TGFβ targeting CAR-T cells||Phase 1|
- Choose appropriate patients with advanced hepatocellular carcinoma,with written consent for this study;
- Perform biopsy to determine the expression of GPC3 of the tumor by western blotting or IHC;
- Collect blood from the patients and isolate mononuclear cells, activate the T cells and transfect the T cells with GPC3/TGFβ targeting CAR (or/and scfv/cytokines-secreting), amplify the number of transfected T cells as needed, test the quality and killing activity of the GPC3/TGFβ-CART cells and then transplant back the patients via systemic or local infusions (via artery or intra-tumor), and follow up closely to collect related results as needed;
- To enhance the killing capability, CD4+ T cells are genetically engineered to express TGFβ-CAR and secret IL7/CCL19 and/or SCFVs against PD1/CTLA4/Tigit; CD8+T cells are constructed to express GPC3-DAP10-CAR with knockdown of PD1/HPK1;
- Evaluate the clinical results as needed.
- Will also perform the similar clinical trial on lung squamous carcinoma with the GPC3 expression.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||CAR-T Cell Targeting GPC3 for Immunotherapy of Hepatocellular Carcinoma: Phase I Clinical Trial|
|Actual Study Start Date :||July 1, 2017|
|Estimated Primary Completion Date :||August 1, 2022|
|Estimated Study Completion Date :||August 1, 2024|
CAR-T cell therapy group
Appropriate patients who could benefit from the GPC3 and TGFβ targeting CAR-T cell therapy against HCC are chosen to be the CAR-T cell therapy group.
Biological: GPC3 and/or TGFβ targeting CAR-T cells
Engineering GPC3 or/and TGFβ targeting CAR combined with/or without IL7/CCL19 and/or scfv against PD1/CTLA4/Tigit secreting vector into T cells with knockdown of PD1/HPK1, which are isolated from patients with advanced HCC, and then transfusing them back the patients.
- Number of Patients with Dose Limiting Toxicity [ Time Frame: three months ]A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the GPC3-T2-CAR T cells, which is irreversible, or life threatening or hematologic or non-hematologic Grade 3-5.
- Percent of Patients with best response as either complete remission or partial remission. [ Time Frame: three months ]Response rates will be estimated as the percent of patients whose best response is either complete remission or partial remission by combining the data from the patients. To compare with historical data, a 95% confidence interval will be calculated for the response rate.
- Median CAR-T cell persistence [ Time Frame: Five years ]Median CAR-T cell persistence will be measured by quantitative rt-PCR.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03198546
|Contact: Zhenfeng Zhang, MD,PhDemail@example.com|
|Contact: Peng Li, PhD||+86 20 firstname.lastname@example.org|
|The First Affiliated Hospital of Sun Yat-sen University||Recruiting|
|Guangzhou, Guangdong, China, 510072|
|Contact: Xianhong Xiang, MD,PHD|
|Contact: Yonghui Huang, MD,PHD|
|The Second Affiliated Hospital of Guangzhou Medical University||Recruiting|
|Guangzhou, Guangdong, China, 510260|
|Contact: Zhenfeng Zhang, MD,PhD +86-020-34153532 email@example.com|
|Contact: Deji Chen, MD,PhD +86-020-34153532 firstname.lastname@example.org|
|Principal Investigator:||Zhenfeng Zhang, MD,PhD||Second Affiliated Hospital of Guangzhou Medical University|