Center for Cell and Gene Therapy, Houston Methodist, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Street, Suite 1770, Houston, TX, 77030, USA.
Adv Exp Med Biol. 2014;804:323-40. doi: 10.1007/978-3-319-04843-7_18.
T-cell immunotherapy may offer an approach to improve outcomes for patients with osteosarcoma, who fail current therapies. In addition, it has the potential to reduce treatment-related complications for all patients. Generating tumor-specific T cells with conventional antigen presenting cells ex vivo is time consuming and often results in T-cell products with a low frequency of tumor-specific T cells. In addition, the generated T cells remain sensitive to the immunosuppressive tumor microenvironment. Genetic modification of T cells is one strategy to overcome these limitations. For example, T cells can be genetically modified to render them antigen specific, resistant to inhibitory factors, or increase their ability to home to tumor sites. Most genetic modification strategies have only been evaluated in preclinical models, however early phase clinical trials are in progress. In this chapter we review the current status of gene-modified T-cell therapy with special focus on osteosarcoma, highlighting potential antigenic targets, preclinical and clinical studies, and strategies to improve current T-cell therapy approaches.
T 细胞免疫疗法可能为那些对现有疗法无效的骨肉瘤患者提供一种改善预后的方法。此外，它还有可能降低所有患者的治疗相关并发症。用传统抗原呈递细胞在体外生成肿瘤特异性 T 细胞耗时耗力，而且通常导致肿瘤特异性 T 细胞的频率较低。此外，生成的 T 细胞仍然对免疫抑制性肿瘤微环境敏感。T 细胞的基因修饰是克服这些限制的一种策略。例如，T 细胞可以经过基因修饰，使其具有抗原特异性、对抑制因子有抗性，或增强其向肿瘤部位归巢的能力。然而，大多数基因修饰策略仅在临床前模型中进行了评估，早期的临床试验正在进行中。在这一章中，我们将特别关注骨肉瘤，综述基因修饰 T 细胞疗法的现状，突出潜在的抗原靶点、临床前和临床研究，以及改善当前 T 细胞治疗方法的策略。
