肿瘤细胞治疗研究
英文原题：CD98 heavy chain protein is overexpressed in non-small cell lung cancer and is a potential target for CAR T-cell therapy.
这些结果提示，R8H283 CAR T 细胞可能成为 NSCLC 的新治疗工具，尽管未来应仔细检测肿瘤外反应性。
嵌合抗原受体（CAR）T细胞对血液系统恶性肿瘤有效，但对非小细胞肺癌（NSCLC）等实体瘤疗效较弱，原因之一是已发现的NSCLC细胞特异性表面靶点较少。本文报告CD98重链（hc）蛋白在NSCLC细胞表面过表达，可作为CAR-T治疗NSCLC的潜在靶点。研究者筛选了针对NSCLC细胞系制备的超过10,000个单克隆抗体，发现H2A011可结合NSCLC细胞但不结合正常肺上皮细胞，并识别CD98hc。推测H2A011在活化T细胞上反应性较强，未能成功建立其来源的CAR-T细胞。随后研究者成功开发了来源于抗CD98hc单克隆抗体R8H283的CAR-T细胞；该抗体已证实不会与正常造血细胞及部分正常组织表达的CD98hc糖型反应。R8H283可特异性识别15例患者中的6例NSCLC细胞。R8H283来源CAR-T细胞在NSCLC异种移植体内模型中表现出显著抗肿瘤作用。结果提示，R8H283 CAR-T细胞可能成为NSCLC的新型治疗工具，但未来仍需谨慎评估其对肿瘤外组织的反应。
Chimeric antigen receptor (CAR) T cells are effective against hematological cancers, but are less effective against solid tumors such as non-small cell lung cancer (NSCLC). One of the reasons is that only a few cell surface targets specific for NSCLC cells have been identified. Here, we report that CD98 heavy chain (hc) protein is overexpressed on the surface of NSCLC cells and is a potential target for CAR T cells against NSCLC. Screening of over 10,000 mAb clones raised against NSCLC cell lines showed that mAb H2A011 bound to NSCLC cells but not normal lung epithelial cells. H2A011 recognized CD98hc. Although CAR T cells derived from H2A011 could not be established presumably due to the high level of H2A011 reactivity in activated T cells, those derived from the anti-CD98hc mAb R8H283, which had been shown to lack reactivity with CD98hc glycoforms expressed on normal hematopoietic cells and some normal tissues, were successfully developed. R8H283 specifically reacted with NSCLC cells in six of 15 patients. R8H283-derived CAR T cells exerted significant anti-tumor effects in a xenograft NSCLC model in vivo. These results suggest that R8H283 CAR T cells may become a new therapeutic tool for NSCLC, although careful testing for off-tumor reactivity should be performed in the future.
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