决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Chimeric Antigen Receptor T Cells: Immunotherapy for the Treatment of Leukemia, Lymphoma, and Myeloma.
在通过基因改造表达嵌合抗原受体(CAR)的 T 细胞免疫治疗中,从患者体内提取自体淋巴细胞,经基因改造获得 CAR-T 细胞,再回输到患者体内攻击癌细胞。
在嵌合抗原受体(CAR)T 细胞免疫疗法中,先从患者体内提取自体淋巴细胞,经基因改造制成 CAR-T 细胞,再回输患者体内以攻击癌细胞。这种疗法在 CD19 阳性白血病和淋巴瘤领域取得成功,已获批用于治疗非霍奇金淋巴瘤、急性淋巴细胞白血病和多发性骨髓瘤。CAR 是将抗体特异性与 T 细胞细胞毒性相结合的蛋白质。临床治疗相关的常见毒性在临床前试验中未能预测,包括细胞因子释放综合征、神经毒性和血细胞减少;这些毒性通常可逆。该领域面临的主要挑战之一是治疗费用高昂,因此必须优先探索降低成本的方法。此外,仍需解决并非所有患者都能获得产品,以及治疗启动等待时间长的问题。本综述旨在介绍 CAR-T 细胞结构的发展、截至目前已获批的疗法、相关毒性,以及 CAR-T 作为免疫疗法的优势与局限。
In immunotherapy with T cells genetically modified to express chimeric antigen receptors (CAR), autologous lymphocytes are extracted from the patient, genetically modified to obtain CAR-T cells, and reintroduced into the patient to attack cancer cells. The success of this therapy has been achieved in the area of CD19-positive leukemias and lymphomas, being approved for the treatment of non-Hodgkin's lymphomas, acute lymphoblastic leukemia, and multiple myeloma. CARs are proteins that combine antibody specificity with T-cell cytotoxicity. The most common toxicities associated with therapy were not predicted by preclinical testing and include cytokine release syndrome, neurotoxicity, and cytopenias. These toxicities are usually reversible. One of the main challenges facing the field is the high economic cost that therapy entails, so the search for ways to reduce this cost must be a priority. In addition, other challenges to overcome include the situation that not all patients are supplied with the product and the existence of long waiting times for the start of therapy. The aim of this review is to present the development of the structure of CAR-T cells, the therapies approved to date, the toxicity associated with them, and the advantages and limitations that they present as immunotherapy.
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