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:Immunotherapies for hepatocellular carcinoma.
肝细胞癌(HCC)的病例正在迅速增加。
肝细胞癌(HCC)的病例正在迅速增加。这在西方世界尤为明显,其原因在于生活方式相关危险因素导致的慢性肝病发病率不断上升,以及普通人群缺乏既定的筛查规划。传统上,HCC的根治性/治愈性治疗选择,包括肝移植和手术切除,仅保留给少数表现为早期癌症的患者。对于晚期疾病患者,直到最近,Sorafenib和Lenvatinib是唯一获批的全身性治疗药物,且仅提供有限的生存获益,代价是众多潜在副作用。近年来癌症免疫治疗领域的科学进展重新点燃了对晚期HCC的显著兴趣,以满足这一明显未被满足的临床需求领域。这促成了Atezolizumab/Bevacizumab联合方案在晚期HCC一线治疗中的成功及近期监管批准,其依据是2019年IMbrave150临床试验的结果,目前还有更多免疫检查点抑制剂正在晚期临床试验中进行测试。此外,其他癌症免疫疗法,包括CAR-T 细胞、树突状细胞疫苗和溶瘤病毒,也正处于早期临床试验阶段,用于晚期HCC的治疗。本综述将总结已用于和目前正在开发中的晚期HCC全身性治疗的主要方法、其优势、缺点,以及对这一革命性治疗领域在可预见的未来将继续走向何方的预测。
Cases of hepatocellular carcinoma (HCC) are rapidly rising. This is particularly the case in the Western world, as a result of increasing rates of chronic liver disease, secondary to lifestyle-associated risk factors and the lack of an established screening programme for the general population. Traditionally, radical/curative treatment options for HCC, including liver transplantation and surgical resection are reserved for the minority of patients, presenting with an early stage cancer. For patients with advanced disease, Sorafenib and Lenvatinib were, until recently, the only licensed systemic treatments, and provided only limited survival benefits at the cost of a multitude of potential side effects. Recent scientific advances in the field of cancer immunotherapy have renewed significant interest in advanced HCC, in order to fulfil this apparent area of unmet clinical need. This has led to the success and recent regulatory approval of an Atezolizumab/Bevacizumab combination for the first-line treatment of advanced HCC following results from the IMbrave150 clinical trial in 2019, with further immune checkpoint inhibitors currently undergoing testing in advanced clinical trials. Furthermore, other cancer immunotherapies, including chimeric antigen receptor T-cells, dendritic cell vaccines and oncolytic viruses are also in early stage clinical trials, for the treatment of advanced HCC. This review will summarise the major approaches that have been and are currently in development for the systemic treatment of advanced HCC, their advantages, drawbacks, and predictions of where this revolutionary treatment field will continue to travel for the foreseeable future.
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