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:Journey of CAR T‑cells: Emphasising the concepts and advancements in breast cancer (Review).
Journey of CAR T‑cells: Emphasising the concepts and advancements in breast cancer (Review).
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癌症是全球死亡率上升的主要且突出原因之一,每年造成近1,000万人死亡。人们已开发针对癌性肿瘤的多种治疗方法,但仍需在细胞和遗传层面开发有效疗法。免疫治疗可使难治性恶性肿瘤患者获得持久缓解,展现出良好前景。近期临床试验显示,基因改造T淋巴细胞可治疗实体瘤、血液系统恶性肿瘤及复发/难治性B细胞恶性肿瘤,这种疗法称为CAR-T 细胞疗法。该疗法通过白细胞去除术分离T淋巴细胞,并经基因工程构建CAR。无需主要组织相容性复合体参与,这些工程化受体即可通过直接与肿瘤抗原结合来裂解恶性组织。临床前及临床研究还显示,CAR-T 有望治疗转移性、三阴性及HER2阳性乳腺癌。
然而,独特毒性会对受体作用机制产生负面影响,包括细胞因子释放综合征、靶向肿瘤或肿瘤外组织识别、神经毒性、过敏反应、乳腺癌中的抗原逃逸,以及实体瘤中的免疫抑制性肿瘤微环境。本文依据临床前和临床试验数据,探讨CAR-T 免疫治疗潜力及其杀伤肿瘤细胞的机制,并更新降低毒性的策略,这些策略有望改善或拓展乳腺癌治疗效果。
Cancer is the primary and one of the most prominent causes of the rising global mortality rate, accounting for nearly 10 million deaths annually. Specific methods have been devised to cure cancerous tumours. Effective therapeutic approaches must be developed, both at the cellular and genetic level. Immunotherapy offers promising results by providing sustained remission to patients with refractory malignancies.
Genetically modified T lymphocytic cells have emerged as a novel therapeutic approach for the treatment of solid tumours, haematological malignancies, and relapsed/refractory B lymphocyte malignancies as a result of recent clinical trial findings; the treatment is referred to as chimeric antigen receptor T cell therapy (CAR T cell therapy).
Leukapheresis is used to remove T lymphocytes from the leukocytes, and CARs are created through genetic engineering. Without the aid of a major histocompatibility complex, these genetically modified receptors lyse malignant tissues by interacting directly with the carcinogen.
Additionally, the outcomes of preclinical and clinical studies reveal that CAR T cell therapy has proven to be a potential therapeutic contender against metastatic breast cancer (BCa), triple negative, and HER 2+ve BCa. Nevertheless, unique toxicities, including (cytokine release syndrome, on/off target tumour recognition, neurotoxicities, anaphylaxis, antigen escape in BCa, and the immunosuppressive tumour microenvironment in solid tumours, negatively impact the mechanism of action of these receptors.
In this review, the potential of CAR T cell immunotherapy and its method of destroying tumour cells is explored using data from preclinical and clinical trials, as well as providing an update on the approaches used to reduce toxicities, which may improve or broaden the effectiveness of the therapies used in BCa.
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