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

NCT ID: NCT06904859

Last Updated: 2025-04-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-01
• Study Completion Date: 2020-12-30

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.

Conditions

Acute Myeloid Leukemia (AML)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AML patients group

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

Group Type: EXPERIMENTAL

TCR-T Cells Injection

Intervention Type: BIOLOGICAL

The TCR sequences of AML patients were analyzed by next generation sequencing to find the specific TCR clone against leukemia，then TCR gene-modified T cells were infused back into the patients

Interventions

TCR-T Cells Injection

The TCR sequences of AML patients were analyzed by next generation sequencing to find the specific TCR clone against leukemia，then TCR gene-modified T cells were infused back into the patients

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Shenzhen University General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Shenzhen University General Hospital

Shenzhen, Guangdong, China

Countries

China

Other Identifiers

HEM-ONCO-029

Identifier Type: -

Identifier Source: org_study_id