Arndt Claudia, Bachmann Michael, Bergmann Ralf, Berndt Nicole, Feldmann Anja, Koristka Stefanie
Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Dresden, Germany.
German Cancer Consortium (DKTK), partner site Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany.
J Labelled Comp Radiopharm. 2019 Jun 30;62(8):533-540. doi: 10.1002/jlcr.3727. Epub 2019 Jun 6.
More than hundred years ago, Paul Ehrlich postulated that our immune system should be able to recognize tumor cells. Just recently, the development of check point inhibitors, bispecific antibodies, and T cells genetically modified to express chimeric antigen receptors (CARs) underlines the true power of our immune system. T cells genetically modified with CARs can lead to complete remission of malignant hematologic diseases. However, they can also cause life-threatening side effects. In case of cytokine release syndrome, tumor lysis syndrome, or deadly side effects on the central nervous system, an emergency shut down of CAR T cells is needed. Targeting of tumor-associated antigens that are also expressed on vital tissues require a possibility to repeatedly switch the activity of CAR T cells on and off on demand and to follow the treatment by imaging. Theranostic, modular CARs such as the UniCAR system may help to overcome these problems.
一百多年前,保罗·埃利希推测我们的免疫系统应该能够识别肿瘤细胞。就在最近,检查点抑制剂、双特异性抗体以及经过基因改造以表达嵌合抗原受体(CAR)的T细胞的发展,凸显了我们免疫系统的真正力量。用CAR进行基因改造的T细胞可导致恶性血液疾病完全缓解。然而,它们也可能引起危及生命的副作用。在发生细胞因子释放综合征、肿瘤溶解综合征或对中枢神经系统产生致命副作用的情况下,需要紧急关闭CAR T细胞。靶向在重要组织上也表达的肿瘤相关抗原,需要有一种可能性,即根据需要反复开启和关闭CAR T细胞的活性,并通过成像跟踪治疗过程。治疗诊断型模块化CAR,如UniCAR系统,可能有助于克服这些问题。