Klebanoff Christopher A, Rosenberg Steven A, Restifo Nicholas P
Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Nat Med. 2016 Jan;22(1):26-36. doi: 10.1038/nm.4015.
Adoptive transfer of receptor-engineered T cells has produced impressive results in treating patients with B cell leukemias and lymphomas. This success has captured public imagination and driven academic and industrial researchers to develop similar 'off-the-shelf' receptors targeting shared antigens on epithelial cancers, the leading cause of cancer-related deaths. However, the successful treatment of large numbers of people with solid cancers using this strategy is unlikely to be straightforward. Receptor-engineered T cells have the potential to cause lethal toxicity from on-target recognition of normal tissues, and there is a paucity of truly tumor-specific antigens shared across tumor types. Here we offer our perspective on how expanding the use of genetically redirected T cells to treat the majority of patients with solid cancers will require major technical, manufacturing and regulatory innovations centered around the development of autologous gene therapies targeting private somatic mutations.
受体工程化T细胞的过继性转移在治疗B细胞白血病和淋巴瘤患者方面取得了令人瞩目的成果。这一成功激发了公众的想象力，并促使学术和产业研究人员开发类似的“现成”受体，以靶向上皮癌（癌症相关死亡的主要原因）上的共享抗原。然而，使用这种策略成功治疗大量实体癌患者可能并非易事。受体工程化T细胞有可能因对正常组织的靶向识别而导致致命毒性，而且不同肿瘤类型之间真正的肿瘤特异性抗原很少。在此，我们就扩大基因重定向T细胞的应用以治疗大多数实体癌患者所需的重大技术、生产和监管创新发表我们的看法，这些创新主要围绕针对个体体细胞突变的自体基因疗法的开发。
