Screening of Anti-Tumor Drugs that Enhance Antigen Presentation of AML Cells with TCR-Like Antibody.
10.19746/j.cnki.issn.1009-2137.2025.05.011
- Author:
Xiao-Ying YANG
1
;
Bo TANG
1
;
Hui-Hui LIU
1
;
Wei-Wei XIE
1
;
Shuang-Lian XIE
1
;
Wen-Qiong WANG
1
;
Jin WANG
1
;
Shan ZHAO
1
;
Yu-Jun DONG
1
Author Information
1. Department of Hematology, Peking University First Hospital, Beijing 100032, China.
- Publication Type:Journal Article
- Keywords:
acute myeloid leukemia;
antigen processing and presentation machinery;
TCR-like antibody
- MeSH:
Humans;
Leukemia, Myeloid, Acute/immunology*;
Antineoplastic Agents/pharmacology*;
Antigen Presentation/drug effects*;
HLA-A2 Antigen/immunology*;
Receptors, Antigen, T-Cell/immunology*;
Cell Line, Tumor;
Interferon-gamma
- From:
Journal of Experimental Hematology
2025;33(5):1305-1311
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To screen anti-tumor drugs that improve antigen processing and presentation in acute myeloid leukemia (AML) cells.
METHODS:A TCR-like or TCR mimic antibody that can specifically recognize HLA-A*0201:WT1126-134 ( RMFPNAPYL) complex (hereafter referred to as HLA-A2:WT1) was synthesized to evaluate the function of antigen processing and presentation machinery (APM) in AML cells. AML cell line THP1 was incubated with increasing concentrations of IFN-γ, hypomethylating agents (HMA), immunomodulatory drugs (IMiD), proteasome inhibitors (PI) and γ-secretase inhibitors (GSI), followed by measuring of HLA-ABC, HLA-A2 and HLA-A2:WT1 levels by flow cytometry at consecutive time points.
RESULTS:The TCR-like antibody we generated only binds to HLA-A*0201+WT1+ cells, indicating the specificity of the antibody. HLA-A2:WT1 level of THP-1 cells detected with the TCR-like antibody was increased significantly after co-incubation with IFN-γ, showing that the HLA-A2:WT1 TCR like antibody could evaluate the function of APM. Among the anti-tumor agents screened in this study, GSI (LY-411575) and HMA (decitabine and azacitidine) could significantly increase the HLA-A2:WT1 level. The IMiD lenalidomide and pomalidomide could aslo upregulate the expression of HLA-A2:WT1 complex under certain concentrations of the drugs and incubation time. As proteasome inhibitors, carfilzomib could significantly decreased the expression of HLA-A2:WT1, while bortezomib had no significant effect on HLA-A2:WT1 expression.
CONCLUSION:HLA-A2:WT1 TCR-like antibody can effectively reflect the APM function. Some of the anti-tumor drugs can affect the APM function and immunogenicity of tumor cells.
