Jennifer N Brudno, Marcela V Maus, Christian S Hinrichs
{"title":"治疗癌症的 CAR T 细胞和 T 细胞疗法:转化科学评论》。","authors":"Jennifer N Brudno, Marcela V Maus, Christian S Hinrichs","doi":"10.1001/jama.2024.19462","DOIUrl":null,"url":null,"abstract":"<p><strong>Importance: </strong>Chimeric antigen receptor (CAR) T cells are T lymphocytes that are genetically engineered to express a synthetic receptor that recognizes a tumor cell surface antigen and causes the T cell to kill the tumor cell. CAR T treatments improve overall survival for patients with large B-cell lymphoma and progression-free survival for patients with multiple myeloma.</p><p><strong>Observations: </strong>Six CAR T-cell products are approved by the US Food and Drug Administration (FDA) for 6 hematologic malignancies: B-cell acute lymphoblastic leukemia, large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia, and multiple myeloma. Compared with standard chemotherapy followed by stem cell transplant, CAR T cells improved 4-year overall survival in patients with large B-cell lymphoma (54.6% vs 46.0%). Patients with pediatric acute lymphoblastic leukemia achieved durable remission after CAR T-cell therapy. At 3-year follow-up, 48% of patients were alive and relapse free. In people with multiple myeloma treated previously with 1 to 4 types of non-CAR T-cell therapy, CAR T-cell therapy prolonged treatment-free remissions compared with standard treatments (in 1 trial, CAR T-cell therapy was associated with progression-free survival of 13.3 months compared with 4.4 months with standard therapy). CAR T-cell therapy is associated with reversible acute toxicities, such as cytokine release syndrome in approximately 40% to 95% of patients, and neurologic disorders in approximately 15% to 65%. New CAR T-cell therapies in development aim to increase efficacy, decrease adverse effects, and treat other types of cancer. No CAR T-cell therapies are FDA approved for solid tumors, but recently, 2 other T lymphocyte-based treatments gained approvals: 1 for melanoma and 1 for synovial cell sarcoma. Additional cellular therapies have attained responses for certain solid tumors, including pediatric neuroblastoma, synovial cell sarcoma, melanoma, and human papillomavirus-associated cancers. A common adverse effect occurring with these T lymphocyte-based therapies is capillary leak syndrome, which is characterized by fluid retention, pulmonary edema, and kidney dysfunction.</p><p><strong>Conclusions and relevance: </strong>CAR T-cell therapy is an FDA-approved therapy that has improved progression-free survival for multiple myeloma, improved overall survival for large B-cell lymphoma, and attained high rates of cancer remission for other hematologic malignancies such as acute lymphoblastic leukemia, follicular lymphoma, and mantle cell lymphoma. Recently approved T lymphocyte-based therapies demonstrated the potential for improved outcomes in solid tumor malignancies.</p>","PeriodicalId":17196,"journal":{"name":"Journal of the American Medical Association","volume":" ","pages":"1924-1935"},"PeriodicalIF":0.0000,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"CAR T Cells and T-Cell Therapies for Cancer: A Translational Science Review.\",\"authors\":\"Jennifer N Brudno, Marcela V Maus, Christian S Hinrichs\",\"doi\":\"10.1001/jama.2024.19462\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Importance: </strong>Chimeric antigen receptor (CAR) T cells are T lymphocytes that are genetically engineered to express a synthetic receptor that recognizes a tumor cell surface antigen and causes the T cell to kill the tumor cell. CAR T treatments improve overall survival for patients with large B-cell lymphoma and progression-free survival for patients with multiple myeloma.</p><p><strong>Observations: </strong>Six CAR T-cell products are approved by the US Food and Drug Administration (FDA) for 6 hematologic malignancies: B-cell acute lymphoblastic leukemia, large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia, and multiple myeloma. Compared with standard chemotherapy followed by stem cell transplant, CAR T cells improved 4-year overall survival in patients with large B-cell lymphoma (54.6% vs 46.0%). Patients with pediatric acute lymphoblastic leukemia achieved durable remission after CAR T-cell therapy. At 3-year follow-up, 48% of patients were alive and relapse free. In people with multiple myeloma treated previously with 1 to 4 types of non-CAR T-cell therapy, CAR T-cell therapy prolonged treatment-free remissions compared with standard treatments (in 1 trial, CAR T-cell therapy was associated with progression-free survival of 13.3 months compared with 4.4 months with standard therapy). CAR T-cell therapy is associated with reversible acute toxicities, such as cytokine release syndrome in approximately 40% to 95% of patients, and neurologic disorders in approximately 15% to 65%. New CAR T-cell therapies in development aim to increase efficacy, decrease adverse effects, and treat other types of cancer. No CAR T-cell therapies are FDA approved for solid tumors, but recently, 2 other T lymphocyte-based treatments gained approvals: 1 for melanoma and 1 for synovial cell sarcoma. Additional cellular therapies have attained responses for certain solid tumors, including pediatric neuroblastoma, synovial cell sarcoma, melanoma, and human papillomavirus-associated cancers. A common adverse effect occurring with these T lymphocyte-based therapies is capillary leak syndrome, which is characterized by fluid retention, pulmonary edema, and kidney dysfunction.</p><p><strong>Conclusions and relevance: </strong>CAR T-cell therapy is an FDA-approved therapy that has improved progression-free survival for multiple myeloma, improved overall survival for large B-cell lymphoma, and attained high rates of cancer remission for other hematologic malignancies such as acute lymphoblastic leukemia, follicular lymphoma, and mantle cell lymphoma. 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引用次数: 0
摘要
重要性:嵌合抗原受体(CAR)T细胞是经过基因工程改造的T淋巴细胞,它能表达一种合成受体,这种受体能识别肿瘤细胞表面的抗原,并使T细胞杀死肿瘤细胞。CAR T疗法可改善大B细胞淋巴瘤患者的总生存期和多发性骨髓瘤患者的无进展生存期:美国食品和药物管理局(FDA)已批准 6 种 CAR T 细胞产品用于治疗 6 种血液系统恶性肿瘤:B细胞急性淋巴细胞白血病、大B细胞淋巴瘤、滤泡淋巴瘤、套细胞淋巴瘤、慢性淋巴细胞白血病和多发性骨髓瘤。与标准化疗后进行干细胞移植相比,CAR T细胞提高了大B细胞淋巴瘤患者的4年总生存率(54.6%对46.0%)。小儿急性淋巴细胞白血病患者在接受CAR T细胞治疗后获得了持久缓解。在3年的随访中,48%的患者存活且未复发。对于曾接受过 1 至 4 种非 CAR T 细胞疗法治疗的多发性骨髓瘤患者,与标准疗法相比,CAR T 细胞疗法延长了无治疗缓解期(在一项试验中,CAR T 细胞疗法的无进展生存期为 13.3 个月,而标准疗法为 4.4 个月)。CAR T 细胞疗法与可逆的急性毒性有关,如约 40% 至 95% 的患者会出现细胞因子释放综合征,约 15% 至 65% 的患者会出现神经系统紊乱。正在开发的新型 CAR T 细胞疗法旨在提高疗效、减少不良反应并治疗其他类型的癌症。目前还没有 CAR T 细胞疗法获得 FDA 批准用于治疗实体瘤,但最近有两种基于 T 淋巴细胞的疗法获得了批准:一种用于治疗黑色素瘤,另一种用于治疗滑膜细胞肉瘤。其他细胞疗法也对某些实体瘤产生了反应,包括小儿神经母细胞瘤、滑膜细胞肉瘤、黑色素瘤和人类乳头状瘤病毒相关癌症。这些基于 T 淋巴细胞的疗法常见的不良反应是毛细血管渗漏综合征,其特点是体液潴留、肺水肿和肾功能障碍:CAR T细胞疗法是美国食品及药物管理局(FDA)批准的一种疗法,它能改善多发性骨髓瘤的无进展生存期,改善大B细胞淋巴瘤的总生存期,并使急性淋巴细胞白血病、滤泡淋巴瘤和套细胞淋巴瘤等其他血液系统恶性肿瘤的癌症缓解率达到很高水平。最近获批的基于 T 淋巴细胞的疗法显示出改善实体瘤恶性肿瘤治疗效果的潜力。
CAR T Cells and T-Cell Therapies for Cancer: A Translational Science Review.
Importance: Chimeric antigen receptor (CAR) T cells are T lymphocytes that are genetically engineered to express a synthetic receptor that recognizes a tumor cell surface antigen and causes the T cell to kill the tumor cell. CAR T treatments improve overall survival for patients with large B-cell lymphoma and progression-free survival for patients with multiple myeloma.
Observations: Six CAR T-cell products are approved by the US Food and Drug Administration (FDA) for 6 hematologic malignancies: B-cell acute lymphoblastic leukemia, large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia, and multiple myeloma. Compared with standard chemotherapy followed by stem cell transplant, CAR T cells improved 4-year overall survival in patients with large B-cell lymphoma (54.6% vs 46.0%). Patients with pediatric acute lymphoblastic leukemia achieved durable remission after CAR T-cell therapy. At 3-year follow-up, 48% of patients were alive and relapse free. In people with multiple myeloma treated previously with 1 to 4 types of non-CAR T-cell therapy, CAR T-cell therapy prolonged treatment-free remissions compared with standard treatments (in 1 trial, CAR T-cell therapy was associated with progression-free survival of 13.3 months compared with 4.4 months with standard therapy). CAR T-cell therapy is associated with reversible acute toxicities, such as cytokine release syndrome in approximately 40% to 95% of patients, and neurologic disorders in approximately 15% to 65%. New CAR T-cell therapies in development aim to increase efficacy, decrease adverse effects, and treat other types of cancer. No CAR T-cell therapies are FDA approved for solid tumors, but recently, 2 other T lymphocyte-based treatments gained approvals: 1 for melanoma and 1 for synovial cell sarcoma. Additional cellular therapies have attained responses for certain solid tumors, including pediatric neuroblastoma, synovial cell sarcoma, melanoma, and human papillomavirus-associated cancers. A common adverse effect occurring with these T lymphocyte-based therapies is capillary leak syndrome, which is characterized by fluid retention, pulmonary edema, and kidney dysfunction.
Conclusions and relevance: CAR T-cell therapy is an FDA-approved therapy that has improved progression-free survival for multiple myeloma, improved overall survival for large B-cell lymphoma, and attained high rates of cancer remission for other hematologic malignancies such as acute lymphoblastic leukemia, follicular lymphoma, and mantle cell lymphoma. Recently approved T lymphocyte-based therapies demonstrated the potential for improved outcomes in solid tumor malignancies.
期刊介绍:
JAMA, published continuously since 1883, is an international peer-reviewed general medical journal. JAMA is a member of the JAMA Network, a consortium of peer-reviewed, general medical and specialty publications.