Progress of chimeric antigen receptor T cell combined with bcl-2 inhibitors for hematological malignancies
10.3760/cma.j.cn115356-20241021-00154
- VernacularTitle:嵌合抗原受体T细胞联合bcl-2抑制剂治疗血液肿瘤的研究进展
- Author:
Qiaolin LIU
1
;
Jia XU
;
Chenggong LI
;
Heng MEI
Author Information
1. 华中科技大学同济医学院附属协和医院血液科，武汉 430022
- Keywords:
Chimeric antigen receptor T cell;
Genes, bcl-2;
Hematologic neoplasms;
Immunotherapy
- From:
Journal of Leukemia & Lymphoma
2025;34(2):114-117
- CountryChina
- Language:Chinese
-
Abstract:
Chimeric antigen receptor-T (CAR-T) cell therapy has achieved remarkable efficacies in the treatment of B-cell leukemia/lymphoma and multiple myeloma (MM). Nevertheless, how to maintain a sustainable remission remains a significant concern. One of the underlying factors for the recurrence after CAR-T cell therapy is the acquired resistance in tumor cells to apoptosis. bcl-2 protein belongs to the anti-apoptotic protein family and plays a key role in regulating endogenous apoptosis. The overexpression of bcl-2 indicates a poor prognosis in hematological malignancies such as chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML) and MM. BH3 is a key protein domain involved in the process of programmed cell death, and bcl-2 inhibitors promote tumor cell apoptosis by competitively binding to BH3. bcl-2 inhibitors have been previously verified to sensitize tumor cells to the cytotoxicity of CAR-T cell. This paper reviews the preclinical and clinical results of CAR-T cell in combination with bcl-2 inhibitors for treatment of hematologic malignancies, aiming to intricate molecular mechanisms of the synergistic effect of CAR-T cell combined with bcl-2 inhibitors and further to improve the efficacy of tumor immunotherapy.
