TCR Therapeutics, Cambridge, Massachusetts.
Mol Cancer Ther. 2019 Mar;18(3):498-506. doi: 10.1158/1535-7163.MCT-18-1070.
Adoptive transfer of T cells engineered with synthetic receptors is emerging as a new pillar in the treatment of cancer. The adoptive cell therapy furthest along in clinical development is the engineering of T cells to express chimeric antigen receptors (CAR) against the CD19 antigen. Several platforms have shown remarkable activity in patients with relapsed or refractory B-cell malignancies. In 2017, the FDA approved the first CAR T cell products tisagenlecleucel (Kymriah, Novartis) and axicabtagene ciloleucel (Yescarta, Gilead), and others are expected to follow shortly. Despite their activity, CAR T cell approaches have limitations that will need to be addressed, including excessive toxicity, relapses mediated via antigen escape, difficulties overcoming the suppressive tumor microenvironment, high manufacturing costs and retail prices, and patient access, among others. The CAR T cell product that better addresses those challenges will obtain a critical competitive advantage.
采用合成受体工程改造的 T 细胞进行过继转移，正在成为癌症治疗的新支柱。在临床开发中走得最远的过继细胞疗法是设计表达嵌合抗原受体（CAR）的 T 细胞，以靶向 CD19 抗原。有几种平台在复发或难治性 B 细胞恶性肿瘤患者中显示出显著的疗效。2017 年，FDA 批准了首批 CAR T 细胞产品 tisagenlecleucel（Kymriah，诺华）和 axicabtagene ciloleucel（Yescarta，吉利德），预计不久后还会有更多产品获批。尽管这些方法具有活性，但 CAR T 细胞方法存在一些需要解决的局限性，包括过度毒性、通过抗原逃逸介导的复发、克服抑制性肿瘤微环境的困难、高制造成本和零售价格以及患者可及性等。能够更好地应对这些挑战的 CAR T 细胞产品将获得关键的竞争优势。
