在实体瘤抗原异质性的崎岖道路上驾驶 CARs。
Driving CARs on the uneven road of antigen heterogeneity in solid tumors.
机构信息
Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA; Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
出版信息
Curr Opin Immunol. 2018 Apr;51:103-110. doi: 10.1016/j.coi.2018.03.002. Epub 2018 Mar 16.
Uniform and strong expression of CD19, a cell surface antigen, on cells of B-cell lineage is unique to hematologic malignancies. Tumor-associated antigen (TAA) targets in solid tumors exhibit heterogeneity with regards to intensity and distribution, posing a challenge for chimeric antigen receptor (CAR) T-cell therapy. Novel CAR designs, such as dual TAA-targeted CARs, tandem CARs, and switchable CARs, in conjunction with inhibitory CARs, are being investigated as means to overcome antigen heterogeneity. In addition to heterogeneity in cancer-cell antigen expression, the key determinants for antitumor responses are CAR expression levels and affinity in T cells. Herein, we review CAR T-cell therapy clinical trials for patients with lung or pancreatic cancers, and provide detailed translational strategies to overcome antigen heterogeneity.
在 B 细胞谱系的细胞上，CD19 这种细胞表面抗原的均匀和强烈表达是血液恶性肿瘤所特有的。实体瘤中的肿瘤相关抗原 (TAA) 靶点在强度和分布上存在异质性，这给嵌合抗原受体 (CAR) T 细胞治疗带来了挑战。新型 CAR 设计，如双 TAA 靶向 CAR、串联 CAR 和可切换 CAR，以及抑制性 CAR，正在被研究作为克服抗原异质性的手段。除了癌细胞抗原表达的异质性外，CAR T 细胞中 CAR 表达水平和亲和力是抗肿瘤反应的关键决定因素。在此，我们综述了针对肺癌或胰腺癌患者的 CAR T 细胞治疗临床试验，并提供了克服抗原异质性的详细转化策略。
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