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This is a multi-center, single arm, open-label, phase I study to determine the safety and effectiveness of CMV-TCR-T cell immunotherapy in treating CMV virus infection after allogenic HSCT.
Cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (HSCT) is common and can be lethal without prompt treatment. In this prospective study, HLA-A*02:01/11:01/24:02-restricted CMV-specific T cell receptor (TCR) will be introduced into the T cells of HSCT donors by ex vivo lentiviral transduction to generate CMV-TCR-T cells. An escalated dose ranging from 1×10^3/kg to 5×10^5/kg of CMV-TCR-T cells will be infused into patients with CMV infection. The safety, efficacy, pharmacokinetics and cytokine levels of allogenic CMV-TCR-T cell therapy will be evaluated.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CMV-TCR-T cells | Experimental | The patients with CMV infection after HSCT will receive one to three infusions of donor-derived CMV-TCR-T cells, with the escalated dose ranging from 1×10^3/kg to 5×10^5/kg CMV-TCR-T cells per dose. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CMV-TCR-T cells | Biological | The patients with CMV infection after HSCT will receive one to three doses of donor-derived CMV-TCR-T cells, with the escalated doses including 1×10^3/kg, 1×10^5/kg, and 5×10^5/kg CMV-TCR-T cells per dose. |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse events | Percentage of participants with adverse events. | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Changes of CMV-DNA copies number | Quantitative PCR will be used to determine viral copy numbers in peripheral blood. | 1 year |
| Persistence of CMV-TCR-T cells | Quantitative PCR using primers specific for the gene encoding CMV-TCR will be used to determine the number of circulating CMV-TCR-T cells in peripheral blood post infusion. |
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Inclusion Criteria:
1) Age ≥ 8 years; 2) Understand and voluntarily sign informed consent and are willing to comply with laboratory tests and other research procedures; 3) ≥ 3/6 HLA match with TCR-T cell recipients enrolled; 4) Lymphocyte count = (0.8~4) × 10^9/L; 5) Have sufficient venous circulation, without any symptoms that do not allow blood cell isolation.
Exclusion Criteria:
11. Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data.
12. TCR-T cell donor exclusion criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Daihong Liu | Contact | 86-13681171597 | daihongrm@163.com | |
| Liping Dou | Contact | 86-13681207138 | lipingruirui@163.com |
| Name | Affiliation | Role |
|---|---|---|
| Daihong Liu | Chinese PLA General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Chinese PLA General Hospital | Recruiting | Beijing | Beijing Municipality | 100853 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42220477 | Derived | Tang J, Wen Y, Yang T, Liu Q, Li F, Wang L, Gu Z, Wu Y, Luan S, Ma C, Wei Y, Qian K, Dou L, Liu D. CMV-specific T-cell receptor-engineered T-cell therapy as first-line treatment for CMV reactivation after haploidentical hematopoietic stem cell transplantation: a phase 2 trial. Front Immunol. 2026 May 14;17:1820399. doi: 10.3389/fimmu.2026.1820399. eCollection 2026. | |
| 38184303 |
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| 1 year |
| Ma C, Chen P, Du J, Wang L, Lu N, Sun J, Qilong X, Wang Y, Dou L, Liu DH. Adoptive transfer of CMV-specific TCR-T cells for the treatment of CMV infection after haploidentical hematopoietic stem cell transplantation. J Immunother Cancer. 2024 Jan 6;12(1):e007735. doi: 10.1136/jitc-2023-007735. |