Clinical trial NCT06904859: The Role and Mechanism of TCR-T Cells in Immunotherapy for Acute Myeloid Leukemia
Official title: The Role and Mechanism of TCR-T Cells in Immunotherapy for Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Acute Myeloid Leukemia (AML)
Keywords: Hematologic Diseases
Leukemia
Leukemia, Myeloid
TCR gene-modified T cells
immunotherapy
TCR-T cells
Lead sponsor: Shenzhen University General Hospital
Sponsor class: OTHER
First posted: 2025-04-01
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Decreased AML percentage in blood
timeFrame: From date of initial treatment to the 20 days after TCR-T Cells infusion
Secondary outcomes:
measure: Decreased AML percentage in cerebrospinal fluid
timeFrame: From date of initial treatment to the 20 days after TCR-T Cells infusion
Other outcomes:
Locations:
city: Shenzhen
country: China
facility: Shenzhen University General Hospital
state: Guangdong
Study officials:
References: