The Role and Mechanism of TCR-T Cells in Immunotherapy for Acute Myeloid Leukemia

Early Phase 1

Completed

• Conditions: Acute Myeloid Leukemia (AML)
• Interventions: Biological: TCR-T Cells Injection

• Registration Number: NCT06904859
• Lead Sponsor: Shenzhen University General Hospital

Brief Summary

Acute myeloid leukemia (AML) is the main type of leukemia, accounting for about 60% of all leukemia, with complex pathogenesis and great clinical heterogeneity. Effective targets for AML need to be further developed. We performed next-generation sequencing analysis of the TCR sequence of an AML patient to find the patient's specific TCR clone for leukemia. The rearranged TCR gene stimulated by leukemia antigens was transduced into the patient's own T cells, and the TCR gene-modified T cells (TCR-T) that could specifically recognize leukemia antigens and kill leukemia cells were constructed. Enhancing the specificity and killing activity of T cells can truly achieve individualized treatment for patients. In addition, through TCR sequencing, the TCR sequence database of leukemia patients can be constructed to find the common specific TCR clones for AML among different patients, which can realize the precise treatment of AML.

Detailed Description

Acute myeloid leukemia (AML) is the main type of leukemia, accounting for about 60% of all leukemia, with complex pathogenesis and great clinical heterogeneity. Effective targets for AML need to be further developed. T cell receptor (TCR) is a characteristic marker on the surface of T cells. Stimulated by leukemia cell antigens, TCR can produce specific rearrangement and produce specific T cell clones for leukemia. However, immunosuppressive cells and immunosuppressive molecules in the leukemia microenvironment have inhibitory effects on T cells, which reduce the activity of T cells with specific clone proliferation. The anti-tumor effect was weakened. In order to solve this clinical problem, we performed next-generation sequencing analysis of the TCR sequence of an AML patient to find the patient's specific TCR clone against leukemia. The rearranged TCR gene stimulated by leukemia antigen was transduced into the patient's own T cells. To construct TCR gene-modified T cells (TCR-T) that can specifically recognize leukemia antigens and kill leukemia cells, enhance the specificity and killing activity of T cells, and truly realize the individualized treatment of patients. In addition, through TCR sequencing, the TCR sequence database of leukemia patients can be constructed to find the common specific TCR clones for AML among different patients, which can realize the precise treatment of AML.

Study Timeline

• Study Start: 2019-01-01
• Primary Completion: 2019-12-01
• Study Completion: 2020-12-30
• Status Verified: 2025-03
• Study First Submitted: 2025-03-12
• Study First Submitted QC: 2025-03-25
• Last Update Submitted: 2025-03-25
• Study First Posted: 2025-04-01
• Last Update Posted: 2025-04-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1. Age 18-65 (≥ 18 years old, ≤ 65 years old)
2. gender is not limited
3. Acute myeloid leukemia patients
4. CR(remission phase, white blood cell count > 2×10^9/L after blood picture recovery)
5. After 3-4 courses of chemotherapy (the number of courses is not absolute)
6. Before the next chemotherapy

Exclusion Criteria

1. Transformed acute myeloid leukemia
2. Secondary acute myeloid leukemia
3. Post-transplantation acute myeloid leukemia
4. AML-M3
5. white blood cell count <2×10^9/L
6. More than 8 courses of chemotherapy
7. Combined with other immune-related diseases
8. Pregnancy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
AML patients group	TCR-T Cells Injection	To construct TCR sequence database of acute myeloid leukemia patients, and then to verify the effect and mechanism of immunotherapy in vitro and in mice，then TCR gene-modified T cells were infused back into the patients

Primary Outcome Measures

Name	Time	Method
Decreased AML percentage in blood	From date of initial treatment to the 20 days after TCR-T Cells infusion	TCR-T Cells were infused back into the patients then the decreased percentage of AML tumor cells in blood after infusion was measured

Secondary Outcome Measures

Name	Time	Method
Decreased AML percentage in cerebrospinal fluid	From date of initial treatment to the 20 days after TCR-T Cells infusion	TCR-T Cells were infused back into the patient then the decreased percentage of AML tumor cells in cerebrospinal fluid after infusion was measured

Trial Locations

Locations (1)

Shenzhen University General Hospital; 🇨🇳 Shenzhen, Guangdong, China