Oppermans Natasha, Kueberuwa Gray, Hawkins Robert E, Bridgeman John S
University of Manchester, Manchester, UK.
Immetacyte Ltd., University of Manchester, Manchester, Greater Manchester, UK.
Ther Adv Vaccines Immunother. 2020 Jun 22;8:2515135520933509. doi: 10.1177/2515135520933509. eCollection 2020.
With the advent of immunotherapy as a realistic and promising option for cancer treatment, adoptive cellular therapies are gaining significant interest in the clinic. Whilst the recent successes of chimeric antigen receptor T-cell therapies for haematological malignancies are widely known, they have yet to show great success in solid cancers. However, immune cells transduced with T-cell receptors have been shown to traffic to and exert anti-cancer effects on solid tumour cells with some great successes. In this review, we explore the field of transgenic T-cell receptor immunotherapy, highlighting some of the key clinical trials which have paved the way for this type of cellular immunotherapy. Some trials have shown amazing clinical results, including long-term remissions and minimal toxicity, and can be looked at as an exemplar for this adoptive cell therapy. There have also been key trials where unexpected, fatal, off-tumour toxicity has occurred, and these trials have also been instrumental in shaping safer clinical trials, particularly regarding preclinical testing. In addition to previous trials, we analysed the current clinical trial space for T-cell receptor T-cell therapy, showing which trials are dominating in the clinic and which targets are being prioritised by researchers around the world. By looking at both past and current trials, we have been able to identify key drivers in developing transgenic T-cell receptor immunotherapy for the future.
随着免疫疗法成为一种切实可行且前景广阔的癌症治疗选择，过继性细胞疗法在临床上正引起广泛关注。虽然嵌合抗原受体T细胞疗法在血液系统恶性肿瘤治疗方面最近取得的成功广为人知，但它们在实体癌治疗中尚未取得巨大成功。然而，经T细胞受体转导的免疫细胞已被证明能够迁移至实体肿瘤细胞并对其发挥抗癌作用，且取得了一些重大成功。在本综述中，我们探讨转基因T细胞受体免疫疗法领域，重点介绍一些为这类细胞免疫疗法铺平道路的关键临床试验。一些试验显示出惊人的临床效果，包括长期缓解和极低的毒性，可被视为这种过继性细胞疗法的典范。也有一些关键试验出现了意外的、致命的非肿瘤毒性，这些试验在塑造更安全的临床试验方面也发挥了重要作用，特别是在临床前测试方面。除了以往的试验，我们还分析了目前T细胞受体T细胞疗法的临床试验情况，展示了哪些试验在临床上占据主导地位以及世界各地的研究人员正在优先考虑哪些靶点。通过审视过去和当前的试验，我们得以确定未来开发转基因T细胞受体免疫疗法的关键驱动因素。
