Efficiently Targeting Neuroblastoma With the Combination of Anti-Ror1 Car Nk Cells and N-803 and in Nb Xenografts

Authors

• Yaya Chu, Department of Pediatrics, New York Medical College, Valhalla, NY 10595, USA.
• Gaurav Nayyar, Department of Pediatrics, New York Medical College, Valhalla, NY 10595, USA.
• Meijuan Tian, Department of Pediatrics, New York Medical College, Valhalla, NY 10595, USA.
• Dean A. Lee, Department of Pediatric Hem/Onc/BMT, Nationwide Children's Hospital, Columbus, OH 43205, USA.Follow
• Mehmet F. Ozkaynak, Department of Pediatrics, New York Medical College, Valhalla, NY 10595, USA.
• Jessica Ayala-Cuesta, Department of Pediatrics, New York Medical College, Valhalla, NY 10595, USA.
• Kayleigh Klose, Department of Pediatrics, New York Medical College, Valhalla, NY 10595, USA.
• Keira Foley, Department of Pediatrics, New York Medical College, Valhalla, NY 10595, USA.
• Alyssa S. Mendelowitz, Department of Pediatrics, New York Medical College, Valhalla, NY 10595, USA.
• Wen Luo, Department of Pediatrics, New York Medical College, Valhalla, NY 10595, USA.
• Yanling Liao, Department of Pediatrics, New York Medical College, Valhalla, NY 10595, USA.
• Janet Ayello, Department of Pediatrics, New York Medical College, Valhalla, NY 10595, USA.Follow
• Gregory K. Behbehani, Department of Internal Medicine, Division of Hematology, the Ohio State University; Columbus, OH 43210, USA.
• Stanley Riddell, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
• Tim Cripe, Department of Pediatric Hem/Onc/BMT, Nationwide Children's Hospital, Columbus, OH 43205, USA.
• Mitchell S. Cairo, Department of Pediatrics, New York Medical College, Valhalla, NY 10595, USA.Follow

Author Type(s)

Faculty, Resident/Fellow

DOI

10.1016/j.omton.2024.200820

Journal Title

Molecular Therapy. Oncology

First Page

200820

Document Type

Article

Publication Date

6-20-2024

Department

Pediatrics

Keywords

IL-15 superagonist, MT: Regular Issue, ROR1, chimerical antigen receptor, cytotoxicity, expanded natural killer cells, neuroblastoma, targeted immunotherapy

Abstract

The prognosis for children with recurrent and/or refractory neuroblastoma (NB) is dismal. The receptor tyrosine kinase-like orphan receptor 1 (ROR1), which is highly expressed on the surface of NB cells, provides a potential target for novel immunotherapeutics. Anti-ROR1 chimeric antigen receptor engineered expanded peripheral blood natural killer (anti-ROR1 CAR exPBNK) cells represent this approach. N-803 is an IL-15 superagonist with enhanced biological activity. In this study, we investigated the and anti-tumor effects of anti-ROR1 CAR exPBNK cells with or without N-803 against ROR1 NB models. Compared to mock exPBNK cells, anti-ROR1 CAR exPBNK cells had significantly enhanced cytotoxicity against ROR1 NB cells, and N-803 further increased cytotoxicity. High-dimensional analysis revealed that N-803 enhanced Stat5 phosphorylation and Ki67 levels in both exPBNK and anti-ROR1 CAR exPBNK cells with or without NB cells. anti-ROR1 CAR exPBNK plus N-803 significantly ( < 0.05) enhanced survival in human ROR1 NB xenografted NSG mice compared to anti-ROR1 CAR exPBNK alone. Our results provide the rationale for further development of anti-ROR1 CAR exPBNK cells plus N-803 as a novel combination immunotherapeutic for patients with recurrent and/or refractory ROR1 NB.

Recommended Citation

Chu, Y., Nayyar, G., Tian, M., Lee, D. A., Ozkaynak, M. F., Ayala-Cuesta, J., Klose, K., Foley, K., Mendelowitz, A. S., Luo, W., Liao, Y., Ayello, J., Behbehani, G. K., Riddell, S., Cripe, T., & Cairo, M. S. (2024). Efficiently Targeting Neuroblastoma With the Combination of Anti-Ror1 Car Nk Cells and N-803 and in Nb Xenografts. Molecular Therapy. Oncology, 32 (2), 200820. https://doi.org/10.1016/j.omton.2024.200820