Cell-based molecularly targeted therapy: targeting oncoproteins with T cell receptor gene therapy.
Cell-based molecularly targeted therapy: targeting oncoproteins with T cell receptor gene therapy.
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基于细胞的分子靶向治疗：利用 T 细胞受体基因治疗靶向癌蛋白。
DOI：
10.1172/jci120386
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Hinrichs,ChristianS
中科院分区：
文献类型：
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作者：
Hinrichs,ChristianS
由于癌基因驱动癌变并促进癌细胞存活，因此它们是极具吸引力的治疗靶点，并且针对癌基因的小分子已经取得了一些临床成功。虽然许多癌基因目前被认为是“可成药的”，但肿瘤通常会产生治疗耐药性，并且患者很少能通过癌基因特异性治疗而治愈。在本期 JCI 中，Veatch 及其同事描述了一位患有转移性肢端黑色素瘤的患者，在输注针对多种肿瘤抗原（包括 BRAFV600E 驱动突变）的肿瘤浸润 T 细胞后，该患者出现了完全的肿瘤反应。经过基因工程改造的 T 细胞可表达来自患者的抗 BRAFV600ET 细胞受体 (TCR)，证明其能够识别跨越 BRAFV600E 突变的表位。这些发现表明，BRAFV600E 可能通过抗 BRAFV600ET 细胞的过继转移进行治疗。这项研究支持利用 T 细胞免疫疗法靶向致癌驱动因素的新兴治疗模式。
As oncogenes drive carcinogenesis and promote cancer cell survival, they are highly attractive therapeutic targets, and oncogene-targeting small molecules have achieved some clinical success. While many oncogenes are presently considered to be “druggable,” tumors often acquire treatment resistance, and patients are rarely cured in response to oncogene-specific treatment. In this issue of theJCI, Veatch and colleagues describe a patient with metastatic acral melanoma who experienced a complete tumor response following infusion of tumor-infiltrating T cells that targeted multiple tumor antigens, including a BRAFV600Edriver mutation. T cells genetically engineered to express an anti-BRAFV600ET cell receptor (TCR) from the patient demonstrated recognition of an epitope that spanned the BRAFV600Emutation. These findings suggest that BRAFV600Emight be targeted therapeutically with adoptive transfer of anti-BRAFV600ET cells. This research supports the emerging therapeutic paradigm of targeting oncogenic drivers with T cell immunotherapy.