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Evaluation of targetable biomarkers for chimeric antigen receptor T-cell (CAR-T) in the treatment of pancreatic cancer: a systematic review and meta-analysis of preclinical studies.
International Reviews of Immunology ( IF 4.3 ) Pub Date : 2020-06-16 , DOI: 10.1080/08830185.2020.1776274
Maryam Sahlolbei 1, 2 , Mohsen Dehghani 3 , Behghat Kheiri Yeghane Azar 1 , Somayeh Vafaei 1 , G Roviello 4 , Alberto D'Angelo 5 , Zahra Madjd 6 , Jafar Kiani 1
Affiliation  

One of the cutting edge techniques for treating cancer is the use of the patient’s immune system to prevail cancerous disease. The versatility of the chimeric antigen receptor (CAR) T-cell approach in conjugation with promising treatments in haematological cancer has led to countless cases of research literature for the treatment of solid cancer. A systematic search of online databases as well as gray literature and reference lists of retrieved studies were carried out up to March 2019 to identify experimental animal studies that investigated the antigens targeted by CAR T-cell for pancreatic cancer treatment. Studies were evaluated for methodological quality using the SYstematic Review Center for Laboratory Animal Experimentation bias risk tool (SYRCLE’s ROB tool). Pooled cytotoxicity ratio/percentage and 95% confidence intervals were calculated using the inverse-variance method while random-effects meta-analysis was used, taking into account conceptual heterogeneity. Heterogeneity was assessed with the Cochran Q statistic and quantified with the I2 statistic using Stata 13.0. Of the 485 identified studies, 56 were reviewed in-depth with 16 preclinical animal studies eligible for inclusion in the systematic review and 11 studies included in our meta-analysis. CAR immunotherapy significantly increased the cytotoxicity assay (percentage: 65%; 95% CI: 46%, 82%). There were no evidence for significant heterogeneity across studies [P = 0.38 (Q statistics), I2 = 7.14%] and for publication bias. The quality assessment of included studies revealed that the evidence was moderate to low quality and none of studies was judged as having a low risk of bias across all domains. CAR T-cell therapy is effective for pancreatic cancer treatment in preclinical animal studies. Further high-quality studies are needed to confirm our finding and a standard approach of this type of studies is necessary according to our assessment.



中文翻译:

嵌合抗原受体 T 细胞 (CAR-T) 治疗胰腺癌的靶向生物标志物的评估:临床前研究的系统评价和荟萃分析。

治疗癌症的前沿技术之一是利用患者的免疫系统来控制癌症疾病。嵌合抗原受体 (CAR) T 细胞方法与血液癌症治疗有希望的结合的多功能性导致了无数用于治疗实体癌的研究文献案例。截至 2019 年 3 月,对在线数据库以及检索研究的灰色文献和参考列表进行了系统搜索,以确定研究 CAR T 细胞靶向抗原用于胰腺癌治疗的实验动物研究。使用实验室动物实验偏倚风险工具(SYRCLE 的 ROB 工具)的 SYstematic 审查中心评估研究的方法学质量。使用逆方差法计算合并细胞毒性比率/百分比和 95% 置信区间,同时使用随机效应荟萃分析,同时考虑到概念异质性。使用 Cochran 评估异质性Q统计量和使用 Stata 13.0的I 2统计量进行量化。在确定的 485 项研究中,56 项进行了深入审查,其中 16 项临床前动物研究符合纳入系统评价的条件,11 项研究纳入我们的荟萃分析。CAR 免疫疗法显着增加了细胞毒性测定(百分比:65%;95% CI:46%,82%)。没有证据表明研究之间存在显着的异质性 [ P  = 0.38 (Q统计量),I2 = 7.14%] 和发表偏倚。纳入研究的质量评估显示,证据质量为中到低,没有一项研究被判定为所有领域的偏倚风险低。在临床前动物研究中,CAR T 细胞疗法对胰腺癌治疗有效。需要进一步的高质量研究来证实我们的发现,根据我们的评估,此类研究的标准方法是必要的。

更新日期:2020-06-16
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