免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Efficacy of T-Cell Receptor-Based Adoptive Cell Therapy in Cutaneous Melanoma: A Meta-Analysis.
Efficacy of T-Cell Receptor-Based Adoptive Cell Therapy in Cutaneous Melanoma: A Meta-Analysis.
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TCR-T 疗法在抗肿瘤活性和生存方面显示出与 TILs 报道相似的有希望的结果,其中针对癌/睾丸抗原的细胞获益显著更高。由于基于 TCR 的疗法显示出相较于经典 ACT 策略具有巨大潜力的优势,因此有必要在实体癌中开展进一步研究(PROSPERO ID CRD42022328011)。
T细胞受体(TCR-T)疗法基于导入的靶向肿瘤相关抗原(TAA)的TCR表达,该疗法已在皮肤黑色素瘤的多项试验中进行研究。我们进行了一项系统综述和meta分析,旨在评估基于TCR的过继细胞疗法在皮肤黑色素瘤中的主要疗效。
我们检索了PubMed电子数据库,从建库至2022年5月21日。主要终点是汇总的客观缓解率(ORR)和疾病控制率(DCR)。我们进行了logistic回归分析,以确定肿瘤缓解的潜在预测因素。
在187例患者中,50例显示出客观缓解(合并ORR 28%;95% CI,20%-37%),合并DCR为38%(95% CI,27%-50%)。中位PFS为2.9个月(95% CI,1.4-3.1)。接受靶向cancer/testis抗原的TCR-T细胞治疗的患者显示出PFS较高的趋势(HR 0.91,95% CI,0.64-1.3,P = .61),其中,接受靶向NYESO-1的TCR-T治疗的患者显示出显著更高的PFS(HR 0.63,95% CI,0.64-0.98,P = .03)。此外,输注细胞数量与显著更高的肿瘤缓解可能性相关(OR 6.61;95% CI,1.68-21.6;P = .007)。
T-cell receptor (TCR-T) therapies are based on the expression of an introduced TCR targeting a tumor associated antigen (TAA) which has been studied in several trials in cutaneous melanoma. We conducted a systematic review and meta-analysis aiming to assess the primary efficacy of TCR-based adoptive cell therapy in cutaneous melanoma.
We searched through PubMed electronic database from its inception until May 21, 2022. Primary endpoints were pooled objective response rate (ORR) and disease control rate (DCR). We conducted logistic regression analyses to identify potential predictive factors for tumor response.
From 187 patients, 50 showed an objective response (pooled ORR 28%; 95% CI, 20%-37%) and a pooled DCR of 38% (95% CI, 27%-50%). Median PFS was 2, 9 months (95% CI, 1.4-3.1). A trend toward higher PFS was demonstrated for patients treated with cancer/testis antigens targeting TCR-T cells (HR 0.91 95% CI, 0.64-1.3, P = .61) among whom, patients treated with NYESO-1 targeting TCR-T showed a significantly higher PFS (HR 0.63 95% CI, 0.64-0.98, P = .03). In addition, the number of infused cells was associated with a significantly higher likelihood of tumor response (OR 6.61; 95% CI, 1.68-21.6; P = .007).
TCR-T therapy shows promising results in terms of antitumor activity and survival similar to those reported for TILs with a significantly higher benefit for cancer/testis antigens targeting cells. Since TCR-based therapy shows advantages of great potential over classic ACT strategies, further research in solid cancers is warranted (PROSPERO ID CRD42022328011).
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