CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:CAR-T Therapy in Relapsed Refractory Multiple Myeloma.
CAR-T Therapy in Relapsed Refractory Multiple Myeloma.
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多发性骨髓瘤是一种浆细胞肿瘤。蛋白酶体抑制剂、免疫调节药物和抗CD38单克隆抗体的出现改善了患者预后,但仍有部分患者对常规治疗不敏感,或缓解后频繁复发。基于蛋白酶体抑制剂或免疫调节药物的化疗无法有效控制复发/难治性多发性骨髓瘤(RRMM)进展,目前该病治疗尚未形成共识。近年来,CAR-T 细胞疗法显示出良好前景,可快速诱导缓解并改善预后。CAR-T 临床试验中的多数患者为三药难治性骨髓瘤,提示CAR-T 免疫疗法可能克服对新型药物的耐药。由于单一免疫疗法易产生获得性耐药,以新兴免疫疗法为基础的联合治疗或可解决这一问题。尽早达到完全缓解和微小残留病阴性状态有利于患者。本文综述RRMM主要CAR-T 产品,阐释CAR-T 治疗耐药机制及改进方法,总结最可能获益的患者群体以及CAR-T 治疗后疾病复发的挽救治疗,为临床应用提供思路。
Multiple myeloma is a plasma cell neoplasm. The emergence of proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies has improved the prognosis of multiple myeloma patients.
However, some patients are still insensitive to conventional therapy or frequently relapse after remission. Chemotherapy based on proteasome inhibitors or immunomodulatory drugs is ineffective in controlling the progression of relapsed refractory multiple myeloma. No consensus has been reached on treating relapsed refractory multiple myeloma to date. Recently chimeric antigen receptor T cells therapy has shown promising results that could achieve rapid remissions of patients and improve their prognoses.
Additionally, most patients in chimeric antigen receptor T cell clinical trials were triple-refractory multiple myeloma patients, indicating that chimeric antigen receptor T cell immunotherapy could overcome drug resistance to new drugs. Since single immunotherapies are prone to acquired resistance, combination immunotherapies based on emerging immunotherapies may solve this issue. Achieving complete remission and minimal residual disease negative status as soon as possible is beneficial to patients.
This paper reviewed the main chimeric antigen receptor T cell products in relapsed refractory multiple myeloma, and it explained the drug resistance mechanism and improvement methods of chimeric antigen receptor T cells therapy. This review summarized the best beneficiaries of chimeric antigen receptor T cell therapy and the salvage treatment of disease recurrence after chimeric antigen receptor T cell therapy, providing some ideas for the clinical application of chimeric antigen receptor T cells.
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