肿瘤细胞治疗研究
英文原题：ROR2-specific CAR T cells are effective against hematologic and solid tumors and well tolerated in mice.
受体酪氨酸激酶（RTK）样孤儿受体 2（ROR2）因其在致癌信号传导中的作用，已被提名为激酶抑制剂的靶点。
受体酪氨酸激酶样孤儿受体2（ROR2）因参与致癌信号传导而被提议作为激酶抑制剂靶点。本研究显示，ROR2也是血液系统和实体瘤中嵌合抗原受体（CAR）T细胞的靶点。我们发现ROR2在多发性骨髓瘤（MM）中稳定表达，并开发出ROR2-CAR T细胞，可在体内对人MM异种移植瘤产生强效作用。对公开基因表达数据分析发现，在六类癌症中，ROR2表达与患者生存呈负相关，包括低级别胶质瘤、甲状腺癌、胃腺癌、膀胱癌以及乳头状和透明细胞肾细胞癌（ccRCC）。我们在体内外验证了ROR2-CAR T细胞对ccRCC的强效活性。ROR2-CAR T治疗耐受性良好，小鼠未见靶向肿瘤外正常组织毒性，支持ROR2作为可用于CAR-T疗法的癌胚抗原。
Receptor tyrosine kinase (RTK)-like orphan receptor 2 (ROR2) has been nominated as a target for kinase inhibitors due to its role in oncogenic signaling. Here, we show that ROR2 is a target for chimeric antigen receptor (CAR) T cells in hematologic and solid tumors. We show consistent ROR2 expression in multiple myeloma (MM) and developed ROR2-CAR T cells that confer potent activity against human MM xenografts in vivo. We analyzed public gene expression data and reveal an inverse correlation between ROR2 expression and patient survival for six types of cancer, i.e., lower-grade glioma, thyroid carcinoma, stomach adenocarcinoma, bladder cancer, and papillary and clear cell renal cell cancer (ccRCC). We confirm potent activity of ROR2-CAR T cells against ccRCC in vitro and in vivo. Treatment with ROR2-CAR T cells was well tolerated, without signs of on-target off-tumor toxicity in mice, supporting the role of ROR2 as an oncofetal antigen with utility for CAR T cell therapy.
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