Integrating Proteomics and Transcriptomics for Systematic Combinatorial Chimeric Antigen Receptor Therapy of AML.,Cancer Cell

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Integrating Proteomics and Transcriptomics for Systematic Combinatorial Chimeric Antigen Receptor Therapy of AML.
Cancer Cell ( IF 48.8 ) Pub Date : 2017-10-09 , DOI: 10.1016/j.ccell.2017.09.004
Fabiana Perna ₁ , Samuel H Berman ₁ , Rajesh K Soni ₂ , Jorge Mansilla-Soto ₁ , Justin Eyquem ₁ , Mohamad Hamieh ₁ , Ronald C Hendrickson ₂ , Cameron W Brennan ₃ , Michel Sadelain ₁

Affiliation

Chimeric antigen receptor (CAR) therapy targeting CD19 has yielded remarkable outcomes in patients with acute lymphoblastic leukemia. To identify potential CAR targets in acute myeloid leukemia (AML), we probed the AML surfaceome for overexpressed molecules with tolerable systemic expression. We integrated large transcriptomics and proteomics datasets from malignant and normal tissues, and developed an algorithm to identify potential targets expressed in leukemia stem cells, but not in normal CD34+CD38- hematopoietic cells, T cells, or vital tissues. As these investigations did not uncover candidate targets with a profile as favorable as CD19, we developed a generalizable combinatorial targeting strategy fulfilling stringent efficacy and safety criteria. Our findings indicate that several target pairings hold great promise for CAR therapy of AML.

中文翻译：

蛋白质组学和转录组学的整合，用于AML的系统组合嵌合抗原受体治疗。

靶向CD19的嵌合抗原受体（CAR）治疗在急性淋巴细胞白血病患者中已取得了显着成果。为了确定急性髓细胞性白血病（AML）中潜在的CAR靶标，我们探查了AML表面基因组中具有可耐受的全身表达的过表达分子。我们整合了来自恶性组织和正常组织的大型转录组学和蛋白质组学数据集，并开发了一种算法来识别在白血病干细胞中表达的潜在靶标，但在正常CD34 + CD38-造血细胞，T细胞或重要组织中没有表达。由于这些研究并未发现具有与CD19一样出色的特征的候选靶标，因此我们开发了可满足严格疗效和安全性标准的通用组合靶向策略。我们的发现表明，几种靶点配对对AML的CAR治疗具有广阔的前景。

更新日期：2017-10-09

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