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This is a prospective, open label, single arm clinical trial to evaluate the safety and the preliminary efficacy of chimeric antigen receptor-dendritic cell (CAR-DC) in the treatment of advanced solid tumors positive for one of the following antigens: ephrin type-A receptor 2 (EphA2), claudin-18 isoform 2 (CLDN18.2) , trophoblast cell surface antigen 2 (Trop2), human epidermal growth factor receptor 2 (HER2), guanylyl cyclase-C (GCC), glypican-3 (GPC3) and carcinoembryonic antigen (CEA).
Dendritic cell (DC) plays a vital role in T cell priming and anti-tumor immune activation. A novel kind of engineered DC, chimeric antigen receptor-dendritic cell (CAR-DC) can reverse the immune suppression in tumor-microenvironment (TME) to enhance anti-tumor therapy. This is a prospective, open label, single arm clinical trial to evaluate the safety and the preliminary efficacy of CAR-DC in the treatment of advanced solid tumors positive for one of the following antigens: ephrin type-A receptor 2 (EphA2), claudin-18 isoform 2 (CLDN18.2) , trophoblast cell surface antigen 2 (Trop2), human epidermal growth factor receptor 2 (HER2), guanylyl cyclase-C (GCC) , glypican-3 (GPC3) AND carcinoembryonic antigen (CEA). A total number of 10 patients will receive two rounds of intravenous infusions of 30 million CAR-DC at an interval of 14 days and receive follow-up visits after the second round of infusion up to 1 or 2 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| treatment | Experimental | The patients will be treated with CAR-DC infusion. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CAR-DC treatment | Biological | The patients will receive intravenous injection (iv) of 30 million CAR-DC for two rounds at an interval of 14 days. |
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| Measure | Description | Time Frame |
|---|---|---|
| To evaluate the objective response rate (ORR) of CAR-DC therapy | The ORR is evaluated according to Response Evaluation Criteria in Solid Tumours 1.1 (RECIST1.1) . | 2 years |
| To evaluate the disease control rate (DCR) of CAR-DC therapy | The DCR is evaluated according to RECIST1.1 criteria. | 2 years |
| The quality of life assessment of CAR-DC therapy | The quality of life is evaluated according to the Eastern Cooperative Oncology Group (ECOG). | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| To evaluate the cytokine release syndrome (CRS) of CAR-DC therapy | The CRS is evaluated according to National Cancer Institute - the Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 (NCI CTCAE5.0). | 2 years |
| To evaluate the neurotoxicity of CAR-DC therapy |
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Inclusion Criteria:
Aged 18-70, regardless of gender;
Diagnosed as EphA2or Claudin18.2, TROP2, HER2, GCC, GPC-3, CEA positive advanced solid tumors, such as lung cancer, liver cancer, colorectal cancer, gastric cancer, etc; Note: Advanced solid tumors refer to locally advanced (stage III patients) and metastatic advanced (stage IV patients) TNM staging by the American Cancer Society (AJCC).
Immunohistochemical analysis of pathological tissue approves positive expression for one of the following antigens, including EphA2, Claudin18.2, TROP2, HER2, GCC, GPC-3 and CEA, with expression intensity ≥ 2+;
Failed response to standard treatment or unwilling/intolerant to all standard treatment regimens;
Imaging indicates measurable tumor lesions;
ECOG PS score: 0-2;
Expected survival time is greater than 3 months;
Maintaining good organ function and bone marrow reserve capacity:
The patient is willing to enroll and signs a written informed consent form, and is able to undergo diagnosis, treatment, and visits according to the protocol.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Chen Junhui, professor | Contact | +86 138 2316 1919 | chenjhpush@126.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking University Shenzhen Hospital | Shenzhen | Guangdong | 518036 | China |
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Neurotoxicity is evaluated according to NCI CTCAE5.0 |
| 2 years |
| To evaluate the survival time of CAR-DC in patient peripheral blood | The survival time of CAR-DC in patient peripheral blood is analysed by flow cytometry of patient blood samples. | 2 years |