Identification and targeting of protein tyrosine kinase 7 (PTK7) as an immunotherapy candidate for neuroblastoma

• Type of Material: Article
• Authors: Jasmine Y Lee, Emory University; Hunter C Jonus, Emory University; Arhanti Sadanand, Emory University; Gianna M Branella, Emory University; Victor Maximov, Emory University; Suttipong Suttapitugsakul, Georgia Institute of Technology, Atlanta; Matthew J Schniederjan, Emory University; Jenny Shim, Emory University; Andrew Ho, Emory University; Kiran K Parwani, Emory University; Andrew Fedanov, Emory University; Adeiye A Pilgrim, Emory University; Jordan A Silva, Emory University; Robert W Schnepp, Emory University; Christopher B Doering, Emory University; Ronghu Wu, Georgia Institute of Technology, Atlanta, GA, USA; H Trent Spencer, Emory University; Kelly C Goldsmith, Emory University
• Language: English
• Date: 2023-06-20
• Publisher: CELL PRESS
• Publication Version: Final Published Version
• Copyright Statement: © 2024 Elsevier Inc
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.xcrm.2023.101091
• Title of Journal or Parent Work: CELL REPORTS MEDICINE
• Volume: 5
• Issue: 6
• Start Page: 101091
• End Page: 101091
• Keywords: CHILDREN; Cell Biology; Life Sciences & Biomedicine; Science & Technology; GD2; Medicine, Research & Experimental; CELLS; Research & Experimental Medicine; EXPRESSION
• Research Categories: Chemistry, Biochemistry; Health Sciences, Medicine and Surgery; Health Sciences, Oncology

Abstract

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.