Efficiently targeting neuroblastoma with the combination of anti-ROR1 CAR NK cells and N-803 in vitro and in vivo in NB xenografts

Autor: Yaya Chu, Gaurav Nayyar, Meijuan Tian, Dean A. Lee, Mehmet F. Ozkaynak, Jessica Ayala-Cuesta, Kayleigh Klose, Keira Foley, Alyssa S. Mendelowitz, Wen Luo, Yanling Liao, Janet Ayello, Gregory K. Behbehani, Stanley Riddell, Timothy P. Cripe, Mitchell S. Cairo
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Molecular Therapy: Oncology, Vol 32, Iss 2, Pp 200820- (2024)
Druh dokumentu: article
ISSN: 2950-3299
DOI: 10.1016/j.omton.2024.200820
Popis: 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 ex vivo 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 in vitro and in vivo 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. In vivo, anti-ROR1 CAR exPBNK plus N-803 significantly (p
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