Acute Myeloid Leukemia (AML)
Conditions
Keywords
Hematologic Diseases, Leukemia, Leukemia, Myeloid, TCR gene-modified T cells, immunotherapy, TCR-T cells
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.
Interventions
BIOLOGICALTCR-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
Sponsors
Shenzhen University General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
China
Outcome results
None listed