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ALPL-1 is a target for chimeric antigen receptor therapy in osteosarcoma.
Mensali, Nadia; Köksal, Hakan; Joaquina, Sandy; Wernhoff, Patrik; Casey, Nicholas P; Romecin, Paola; Panisello, Carla; Rodriguez, René; Vimeux, Lene; Juzeniene, Asta; Myhre, Marit R; Fåne, Anne; Ramírez, Carolina Castilla; Maggadottir, Solrun Melkorka; Duru, Adil Doganay; Georgoudaki, Anna-Maria; Grad, Iwona; Maturana, Andrés Daniel; Gaudernack, Gustav; Kvalheim, Gunnar; Carcaboso, Angel M; de Alava, Enrique; Donnadieu, Emmanuel; Bruland, Øyvind S; Menendez, Pablo; Inderberg, Else Marit; Wälchli, Sébastien.
Afiliación
  • Mensali N; Translational Research Unit, Department of Cellular Therapy, Oslo University Hospital, Oslo, Norway.
  • Köksal H; Translational Research Unit, Department of Cellular Therapy, Oslo University Hospital, Oslo, Norway.
  • Joaquina S; Translational Research Unit, Department of Cellular Therapy, Oslo University Hospital, Oslo, Norway.
  • Wernhoff P; Translational Research Unit, Department of Cellular Therapy, Oslo University Hospital, Oslo, Norway.
  • Casey NP; Translational Research Unit, Department of Cellular Therapy, Oslo University Hospital, Oslo, Norway.
  • Romecin P; Josep Carreras Leukemia Research Institute, Barcelona, Spain.
  • Panisello C; Red Española de Terapias Avanzadas (TERAV)-Instituto de Salud Carlos III (ISCIII) (RICORS, RD21/0017/0029), Madrid, Spain.
  • Rodriguez R; Josep Carreras Leukemia Research Institute, Barcelona, Spain.
  • Vimeux L; Red Española de Terapias Avanzadas (TERAV)-Instituto de Salud Carlos III (ISCIII) (RICORS, RD21/0017/0029), Madrid, Spain.
  • Juzeniene A; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, Oviedo, Spain.
  • Myhre MR; Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain.
  • Fåne A; Centro de Investigación Biomédica en Red-Oncología (CIBER-ONC), Instituto de Salud Carlos III, Madrid, Spain.
  • Ramírez CC; Université de Paris, Institut Cochin, INSERM, CNRS, Equipe labellisée Ligue Contre le Cancer, F-75014, PARIS, France.
  • Maggadottir SM; Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
  • Duru AD; Translational Research Unit, Department of Cellular Therapy, Oslo University Hospital, Oslo, Norway.
  • Georgoudaki AM; Translational Research Unit, Department of Cellular Therapy, Oslo University Hospital, Oslo, Norway.
  • Grad I; Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital, CSIC, University of Sevilla, CIBER-ONC, 41013, Seville, Spain.
  • Maturana AD; Translational Research Unit, Department of Cellular Therapy, Oslo University Hospital, Oslo, Norway.
  • Gaudernack G; NSU Cell Therapy Institute, Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA.
  • Kvalheim G; NSU Cell Therapy Institute, Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA.
  • Carcaboso AM; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
  • de Alava E; Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
  • Donnadieu E; Laboratory of Animal Cell Physiology, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
  • Bruland ØS; Department of Cancer Immunology, Oslo University Hospital, Oslo, Norway.
  • Menendez P; Translational Research Unit, Department of Cellular Therapy, Oslo University Hospital, Oslo, Norway.
  • Inderberg EM; SJD Pediatric Cancer Center Barcelona, Institut de Recerca Sant Joan de Deu, Barcelona, 08950, Spain.
  • Wälchli S; Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital, CSIC, University of Sevilla, CIBER-ONC, 41013, Seville, Spain.
Nat Commun ; 14(1): 3375, 2023 06 08.
Article en En | MEDLINE | ID: mdl-37291203
Osteosarcoma (OS) remains a dismal malignancy in children and young adults, with poor outcome for metastatic and recurrent disease. Immunotherapies in OS are not as promising as in some other cancer types due to intra-tumor heterogeneity and considerable off-target expression of the potentially targetable proteins. Here we show that chimeric antigen receptor (CAR) T cells could successfully target an isoform of alkaline phosphatase, ALPL-1, which is highly and specifically expressed in primary and metastatic OS. The target recognition element of the second-generation CAR construct is based on two antibodies, previously shown to react against OS. T cells transduced with these CAR constructs mediate efficient and effective cytotoxicity against ALPL-positive cells in in vitro settings and in state-of-the-art in vivo orthotopic models of primary and metastatic OS, without unexpected toxicities against hematopoietic stem cells or healthy tissues. In summary, CAR-T cells targeting ALPL-1 show efficiency and specificity in treating OS in preclinical models, paving the path for clinical translation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Óseas / Osteosarcoma Límite: Child / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: Noruega Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Óseas / Osteosarcoma Límite: Child / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: Noruega Pais de publicación: Reino Unido