Survival rates for sarcoma patients have plateaued in the past few decades and remain especially grim for those with recurrent or metastatic disease. This has prompted investigation into novel immunotherapies for sarcomas, especially after their recent and well-recognized successes in other cancers. One such modality, the Chimeric Antigen Receptor (CAR) T Cell therapy, has shown promising results in treating B-cell lymphoma and acute lymphoblastic leukemia. This novel therapy functions by fusing a specific antibody derived single-chain variable fragment (scFv) with a T-cell which recognizes a specific tumor-associated antigen (TAA). Several sarcoma-associated antigens (SAA) amenable to CAR-T cell treatment have recently emerged with encouraging results. These include human epidermal growth factor receptor 2 (HER2), disialoganglioside (GD2), interleukin 11 Receptor Subunit Alpha (IL-11RA), fibroblast activation protein (FAP), B7-H3, CD44v6, insulin-like growth factor 1 receptor (IGF-1R), and tyrosine kinase orphan-like receptor 1 (ROR1). Given the limitations of current medical therapies, novel treatment strategies are urgently needed. As a sarcoma treatment modality, CAR-T cell therapy is highly promising and continues to draw interest especially as new clinical trials emerge. Here we review recent breakthrough CAR-T cell studies in sarcoma, the targets which define them, and approaches to minimizing host cytotoxicity.

中文翻译：

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肉瘤嵌合抗原受体T（CAR-T）细胞免疫疗法：从机理到潜在的临床应用。

在过去的几十年中，肉瘤患者的存活率一直处于稳定状态，对于那些复发或转移性疾病的患者，其生存率仍然尤其严峻。这促使人们对肉瘤的新型免疫疗法进行了研究，尤其是在它们最近在其他癌症中获得公认的成功之后。一种这样的方式，即嵌合抗原受体（CAR）T细胞疗法，在治疗B细胞淋巴瘤和急性淋巴细胞白血病中显示出令人鼓舞的结果。这种新型疗法通过将特异性抗体衍生的单链可变片段（scFv）与识别特定肿瘤相关抗原（TAA）的T细胞融合来发挥作用。最近出现了几种适用于CAR-T细胞治疗的肉瘤相关抗原（SAA），其结果令人鼓舞。其中包括人类表皮生长因子受体2（HER2），双唾液酸神经节苷脂（GD2），白细胞介素11受体亚基（IL-11RA），成纤维细胞活化蛋白（FAP），B7-H3，CD44v6，胰岛素样生长因子1受体（IGF-1R）和酪氨酸激酶孤儿样受体1（ROR1）。考虑到当前医学疗法的局限性，迫切需要新颖的治疗策略。作为肉瘤的治疗方式，CAR-T细胞疗法非常有前途，并且继续引起人们的兴趣，尤其是随着新的临床试验的出现。在这里，我们回顾了肉瘤中近期突破性的CAR-T细胞研究，定义它们的靶标以及将宿主细胞毒性降至最低的方法。迫切需要新的治疗策略。作为肉瘤的治疗方式，CAR-T细胞疗法非常有前途，并且继续引起人们的兴趣，尤其是随着新的临床试验的出现。在这里，我们回顾了肉瘤中近期突破性的CAR-T细胞研究，定义它们的靶标以及将宿主细胞毒性降至最低的方法。迫切需要新的治疗策略。作为肉瘤的治疗方式，CAR-T细胞疗法非常有前途，并且继续引起人们的兴趣，尤其是随着新的临床试验的出现。在这里，我们回顾了肉瘤中近期突破性的CAR-T细胞研究，定义它们的靶标以及将宿主细胞毒性降至最低的方法。