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kgoldsm@emory.edu

Conceptualization, K.C.G., J.Y.L., H.C.J., H.T.S., and R.W., Methodology, K.C.G., J.Y.L., H.C.J., H.T.S., G.M.B., R.W.S., S.S., and R.W., Investigation, K.C.G., J.Y.L., H.C.J., A.S., V.M., S.S., M.J.S., K.K.P., A.F., A.A.P., J.S., A.H., and J.A.S.; Writing – Original Draft, J.Y.L., K.C.G., H.C.J., and H.T.S.; Writing – Review & Editing, J.Y.L., K.C.G., H.C.J., H.T.S., C.B.D., R.W., and S.S., Visualization, J.Y.L., K.C.G., and H.C.J.; Supervision, K.C.G. and H.T.S.

This research was supported by the Alex’s Lemonade Stand Foundation for Childhood Cancer Reach Award awarded to K.C.G. and H.T.S.; CURE Childhood Cancer through the Aflac Precision Medicine Program awarded to K.C.G.; Curing Kids Cancer awarded to H.T.S.; and the National Institutes of Health under an R01 grant (R01GM118803 to R.W.) and a T32 institutional training grant awarded to Emory University (5T32Hl069769-17 to H.C.J.). We thank the Children’s Healthcare of Atlanta and Emory University Pediatric/Winship Flow Cytometry Core for support with flow cytometry experiments and instrument use, the Winship Cancer Tissue Pathology Core at Emory University for support with IHC experiments, and the Department of Pathology at Children’s Healthcare of Atlanta for support with the development of the pediatric normal tissue microarray. The graphical abstract was created using BioRender.com.

The authors declare no competing interests.

Subjects:

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell Biology
  • Medicine, Research & Experimental
  • Research & Experimental Medicine
  • CELLS
  • EXPRESSION
  • CHILDREN
  • GD2

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

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Journal Title:

CELL REPORTS MEDICINE

Volume:

Volume 5, Number 6

Publisher:

, Pages 101091-101091

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2024 Elsevier Inc

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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