Advances in new approaches for the immunotherapy of acute myeloid leukemia
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摘要: 急性髓系白血病(AML)是不成熟的造血细胞在骨髓内聚集、不断扩增并抑制造血的一类疾病,其核心治疗方案近30年基本保持不变,但疾病的预后及生存率仍不理想。然而,目前针对机体免疫机制的研究使得免疫治疗得到不断完善,因此免疫治疗可能成为今后治疗AML的有效方案,为该病的预后及生存率提供了新的武器。免疫治疗的执行方案包括:异基因造血干细胞移植、靶向治疗(基因工程T细胞、单克隆抗体等)等多种途径,通过不同机制杀伤肿瘤细胞。异基因造血干细胞移植作为AML最有效的治疗,通过免疫介导的移植物抗白血病效应根除白血病细胞,能有效预防AML复发。移植技术和单倍体移植模式进展使得“人人都能进行造血干细胞移植”。靶向治疗,如基因工程T细胞(嵌合抗原受体T细胞)、单克隆抗体、新型双特异性单抗,能特异性杀伤表达特殊抗原的白血病细胞而不伤害正常细胞,将成为AML免疫治疗的新策略。其他如自然杀伤细胞,结合NK细胞治疗可安全、有效降低AML复发风险,此外,增强NK细胞活性可能是今后最佳的白血病治疗方案。虽然现在仍然有部分方案尚处于研究阶段,但免疫治疗将成为今后治疗AML的重要手段。本文将对目前AML免疫治疗的研究进展及相关分子学机制进行综述。Abstract: Acute myeloid leukemia(AML) is a kind of disease of hematopoietic cells in bone marrow immature aggregation,continuous amplification and suppression of hematopoiesis.Its core treatment in recent 30 years remained unchanged,but the survival rate and the prognosis of the disease is still not ideal.However,current research on the immune mechanism of the immune therapy has been perfected,so the immune therapy may be an effective solution in the treatment of AML,provides a new weapon for the prognosis and the survival rate of the disease.The protocols for immunotherapy include allogeneic hematopoietic stem cell transplantation,targeted therapies(gene engineered T cells,monoclonal antibodies,etc.),killing tumor cells through different mechanisms.Allogeneic hematopoietic stem cell transplantation,as the most effective treatment for AML can effectively prevent the recurrence of AML by immune mediated graft versus leukemia effect and eradicate leukemic cells.Advances in transplantation and haploidentical transplantation have enabled everyone to have a stem cell transplant.Targeted therapy,such as genetically engineered T cells(T cells,chimeric antigen receptor) monoclonal antibody,novel bispecific monoclonal antibody can specifically kill specific antigen expression of leukemia cells without harming normal cells will become a new strategy for AML immunotherapy.Other therapies,such as natural killer cells and NK cells,are safe and effective in reducing the risk of AML recurrence.In addition,increasing NK cell activity may be the best treatment for leukemia in the future.Although some programs are still in the study stage,immunotherapy will be an important treatment for AML in the future.This paper will review the current research progress of AML immunotherapy and related molecular mechanism.
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Key words:
- Acute Myeloid Leukemia /
- T lymphocyte /
- Adoptive Immunotherapy
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