肿瘤细胞治疗研究
英文原题：Long-term safety of lentiviral or gammaretroviral gene-modified T cell therapies.
在本研究中，我们评估了来自38项T细胞疗法试验的783名患者的安全性结局，总观察时间超过2，200患者年。
基因治疗的长期风险尚未完全明确。在本研究中，我们评估了来自38项T细胞治疗试验的783例患者的安全性结局，总观察时间超过2,200患者年。这些试验采用整合型γ逆转录病毒或慢病毒载体，将工程化受体递送至靶向HIV-1感染或癌症。18例患者（2.3%）在治疗后发生继发性恶性肿瘤，中位发病时间为1.94年（范围：51天至14年）。在可能的情况下，对偶发肿瘤样本进行了载体拷贝数分析，未发现高水平标记或其他插入性突变迹象。检测到1例T细胞淋巴瘤，但恶性T细胞未被载体整合标记。对176例患者的载体整合位点分析未发现与继发性恶性肿瘤相关的病理性插入，尽管在某些病例中，特定基因（包括抑癌基因）内部或附近的整合与轻度克隆扩增和持续性T细胞存续相关。这些发现凸显了工程化T细胞疗法的安全性。
Long-term risks of gene therapy are not fully understood. In this study, we evaluated safety outcomes in 783 patients over more than 2,200 total patient-years of observation from 38 T cell therapy trials. The trials employed integrating gammaretroviral or lentiviral vectors to deliver engineered receptors to target HIV-1 infection or cancer. Eighteen patients (2.3%) developed secondary malignancies after treatment, with a median onset of 1.94 years (range: 51 d to 14 years). Where possible, incident tumor samples were analyzed for vector copy number, revealing no evidence of high-level marking or other indications of insertional mutagenesis. One T cell lymphoma was detected, but malignant T cells were not marked by vector integration. Analysis of vector integration sites in 176 patients revealed no pathological insertions linked to secondary malignancies, although, in some cases, integration in or near specific genes, including tumor suppressor genes, was associated with modest clonal expansion and sustained T cell persistence. These findings highlight the safety of engineered T cell therapies.
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