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.

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

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