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Efficiently targeting neuroblastoma with the combination of anti-ROR1 CAR NK cells and N-803 in vitro and in vivo in NB xenografts.
Chu, Yaya; Nayyar, Gaurav; Tian, Meijuan; Lee, Dean A; Ozkaynak, Mehmet F; Ayala-Cuesta, Jessica; Klose, Kayleigh; Foley, Keira; Mendelowitz, Alyssa S; Luo, Wen; Liao, Yanling; Ayello, Janet; Behbehani, Gregory K; Riddell, Stanley; Cripe, Tim; Cairo, Mitchell S.
Afiliación
  • Chu Y; Department of Pediatrics, New York Medical College, Valhalla, NY 10595, USA.
  • Nayyar G; Department of Pediatrics, New York Medical College, Valhalla, NY 10595, USA.
  • Tian M; Department of Pediatrics, New York Medical College, Valhalla, NY 10595, USA.
  • Lee DA; Department of Pediatric Hem/Onc/BMT, Nationwide Children's Hospital, Columbus, OH 43205, USA.
  • Ozkaynak MF; Department of Pediatrics, New York Medical College, Valhalla, NY 10595, USA.
  • Ayala-Cuesta J; Department of Pediatrics, New York Medical College, Valhalla, NY 10595, USA.
  • Klose K; Department of Pediatrics, New York Medical College, Valhalla, NY 10595, USA.
  • Foley K; Department of Pediatrics, New York Medical College, Valhalla, NY 10595, USA.
  • Mendelowitz AS; Department of Pediatrics, New York Medical College, Valhalla, NY 10595, USA.
  • Luo W; Department of Pediatrics, New York Medical College, Valhalla, NY 10595, USA.
  • Liao Y; Department of Pediatrics, New York Medical College, Valhalla, NY 10595, USA.
  • Ayello J; Department of Pediatrics, New York Medical College, Valhalla, NY 10595, USA.
  • Behbehani GK; Department of Internal Medicine, Division of Hematology, the Ohio State University; Columbus, OH 43210, USA.
  • Riddell S; Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Cripe T; Department of Pediatric Hem/Onc/BMT, Nationwide Children's Hospital, Columbus, OH 43205, USA.
  • Cairo MS; Department of Pediatrics, New York Medical College, Valhalla, NY 10595, USA.
Mol Ther Oncol ; 32(2): 200820, 2024 Jun 20.
Article en En | MEDLINE | ID: mdl-38933492
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 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 < 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mol Ther Oncol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mol Ther Oncol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos