神经母细胞瘤
癌症研究
免疫疗法
细胞毒性T细胞
酪氨酸激酶
医学
生物
免疫学
体外
细胞培养
受体
内科学
免疫系统
遗传学
生物化学
作者
Jasmine Y. Lee,Hunter C. Jonus,Arhanti Sadanand,Gianna M. Branella,Victor Maximov,Suttipong Suttapitugsakul,Matthew Schniederjan,Jenny Shim,Andrew K.S. Ho,Kiran K. Parwani,Andrew Fedanov,Adeiye A. Pilgrim,Jordan A. Silva,Robert W. Schnepp,Christopher B. Doering,Ronghu Wu,H. Trent Spencer,Kelly C. Goldsmith
标识
DOI:10.1016/j.xcrm.2023.101091
摘要
GD2-targeting immunotherapies have improved survival in children with neuroblastoma, yet on-target, off-tumor toxicities can occur and a subset of patients cease to respond. The majority of neuroblastoma patients who receive immunotherapy have been previously treated with cytotoxic chemotherapy, making it paramount to identify neuroblastoma-specific antigens that remain stable throughout standard treatment. Cell surface glycoproteomics performed on human-derived neuroblastoma tumors in mice following chemotherapy treatment identified protein tyrosine kinase 7 (PTK7) to be abundantly expressed. Furthermore, PTK7 shows minimal expression on pediatric-specific normal tissues. We developed an anti-PTK7 chimeric antigen receptor (CAR) and find PTK7 CAR T cells specifically target and kill PTK7-expressing neuroblastoma in vitro. In vivo, human/murine binding PTK7 CAR T cells regress aggressive neuroblastoma metastatic mouse models and prolong survival with no toxicity. Together, these data demonstrate preclinical efficacy and tolerability for targeting PTK7 and support ongoing investigations to optimize PTK7-targeting CAR T cells for neuroblastoma.
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