Synthetic biology has been transformative to the treatment of advanced hematological malignancies by chimeric antigen receptor (CAR)-engineered T cells. A range of obstacles are now understood to limit the responses of solid epithelial-derived tumors to CAR therapy. For example, inefficient tumor homing and a fortified stroma can restrain the number of CAR-T cells reaching the tumor bed. Upon transendothelial migration across the tumor vasculature, CAR-T cells face a highly suppressive microenvironment that can quickly render them hypofunctional. Safety also remains a critical issue for advancing CAR therapy of solid tumors. Innovative CAR design as well as coengineering and combinatorial treatment strategies with oncolytic adenovirus, radiotherapy, vaccines, chemotherapy, small molecules and monoclonal antibodies hold tremendous potential to support CAR-T cell control of solid tumors, either by directly promoting CAR-T cell function, or/and by re-programming the TME and harnessing the endogenous immune system against the tumor.

中文翻译：

---

所有系统都去了：融合合成生物学和CAR-T细胞疗法的组合治疗。

合成生物学已通过嵌合抗原受体（CAR）改造的T细胞对晚期血液系统恶性肿瘤的治疗进行了转化。现在已经理解了一系列障碍，以限制实体上皮来源的肿瘤对CAR治疗的反应。例如，无效的肿瘤归巢和强化的基质可以限制到达肿瘤床的CAR-T细胞的数量。当跨内皮迁移穿过肿瘤血管时，CAR-T细胞面临高度抑制性的微环境，该环境会使其功能迅速丧失。安全性仍然是推进实体瘤CAR治疗的关键问题。创新的CAR设计以及溶瘤腺病毒，放射疗法，疫苗，化学疗法的联合工程和联合治疗策略，