Approval of the drugtisagenlecleucel(Kymriah;Novartis) by the US Food and Drug Administration (FDA) for the treatment of pediatric and young adult acute lymphoblastic leukemia (ALL) in August 2017 was a landmark in oncology. The science underlying chimeric antigen receptor T cells (CAR-T) heralds a new era of treatment, and the list price of $475 000 for the new drug (delivered as a one-time infusion) definitively shattered oncology drug pricing norms.1 Unlike most cancer therapies that are identical from patient to patient, CAR-T therapies are made by removing the T cells of a patient, genetically modifying them to respond to certain targets expressed on the patient’s cancer cells, and then reinfusing the cells. When the T cells come into contact with the relevant target (for instance, CD19 in the case of ALL), they proliferate while secreting a number of programmed substances including inflammatory cytokines that destroy the cancerous cells. Targeted killing of tumor cells by lymphocytes was first suggested by the graft-vs-leukemia effect in bone marrow transplantation,2 but that effect and the infusion of donor T cells more generally has no effect on solid tumor malignancies or most hematologic cancers. The innovation underlying CAR-T involved exploiting the specificity of antibody-mediated recognition of tumor

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FDA 批准 Tisagenlecleucel

2017 年 8 月，美国食品药品监督管理局（FDA）批准了用于治疗儿童和青年急性淋巴细胞白血病（ALL）的 drugtisagenlecleucel（Kymriah；Novartis）是肿瘤学的一个里程碑。嵌合抗原受体 T 细胞 (CAR-T) 的基础科学预示着治疗的新时代，47.5 万美元的新药（一次性输液）的定价彻底打破了肿瘤药物定价规范。 1 与大多数癌症疗法因患者而异，CAR-T疗法是通过去除患者的T细胞，对其进行基因改造以对患者癌细胞上表达的某些靶标做出反应，然后重新注入细胞来实现的。当 T 细胞与相关目标（例如，ALL 中的 CD19）接触时，它们在分泌许多程序化物质的同时增殖，包括破坏癌细胞的炎性细胞因子。淋巴细胞靶向杀伤肿瘤细胞首先是由骨髓移植中的移植物抗白血病效应提出的，2 但这种效应和供体 T 细胞的输注更普遍地对实体瘤恶性肿瘤或大多数血液系统癌症没有影响。CAR-T 的创新之处在于利用抗体介导的肿瘤识别的特异性 2 但这种影响和供体 T 细胞的输注更普遍地对实体瘤恶性肿瘤或大多数血液系统癌症没有影响。CAR-T 的创新之处在于利用抗体介导的肿瘤识别的特异性 2 但这种影响和供体 T 细胞的输注更普遍地对实体瘤恶性肿瘤或大多数血液系统癌症没有影响。CAR-T 的创新之处在于利用抗体介导的肿瘤识别的特异性