ALPL-1 is a target for chimeric antigen receptor therapy in osteosarcoma.

Autor: 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.; Red Española de Terapias Avanzadas (TERAV)-Instituto de Salud Carlos III (ISCIII) (RICORS, RD21/0017/0029), Madrid, Spain., Panisello C; Josep Carreras Leukemia Research Institute, Barcelona, Spain.; Red Española de Terapias Avanzadas (TERAV)-Instituto de Salud Carlos III (ISCIII) (RICORS, RD21/0017/0029), Madrid, Spain., Rodriguez R; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, Oviedo, Spain.; Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain.; Centro de Investigación Biomédica en Red-Oncología (CIBER-ONC), Instituto de Salud Carlos III, Madrid, Spain., Vimeux L; Université de Paris, Institut Cochin, INSERM, CNRS, Equipe labellisée Ligue Contre le Cancer, F-75014, PARIS, France., Juzeniene A; Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway., Myhre MR; Translational Research Unit, Department of Cellular Therapy, Oslo University Hospital, Oslo, Norway., Fåne A; Translational Research Unit, Department of Cellular Therapy, Oslo University Hospital, Oslo, Norway., Ramírez CC; Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital, CSIC, University of Sevilla, CIBER-ONC, 41013, Seville, Spain., Maggadottir SM; Translational Research Unit, Department of Cellular Therapy, Oslo University Hospital, Oslo, Norway., Duru AD; NSU Cell Therapy Institute, Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA., Georgoudaki AM; NSU Cell Therapy Institute, Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA.; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden., Grad I; Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway., Maturana AD; Laboratory of Animal Cell Physiology, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan., Gaudernack G; Department of Cancer Immunology, Oslo University Hospital, Oslo, Norway., Kvalheim G; Translational Research Unit, Department of Cellular Therapy, Oslo University Hospital, Oslo, Norway., Carcaboso AM; SJD Pediatric Cancer Center Barcelona, Institut de Recerca Sant Joan de Deu, Barcelona, 08950, Spain., de Alava E; Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital, CSIC, University of Sevilla, CIBER-ONC, 41013, Seville, Spain.; Department of Normal and Pathological Cytology and Histology, School of Medicine, University of Seville, 41009, Seville, Spain., Donnadieu E; Université de Paris, Institut Cochin, INSERM, CNRS, Equipe labellisée Ligue Contre le Cancer, F-75014, PARIS, France., Bruland ØS; Department of Oncology, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Menendez P; Josep Carreras Leukemia Research Institute, Barcelona, Spain.; Red Española de Terapias Avanzadas (TERAV)-Instituto de Salud Carlos III (ISCIII) (RICORS, RD21/0017/0029), Madrid, Spain.; CIBER-ONC, ISCIII, Barcelona, Spain.; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.; Department of Biomedicine, School of Medicine, University of Barcelona, Barcelona, Spain., Inderberg EM; Translational Research Unit, Department of Cellular Therapy, Oslo University Hospital, Oslo, Norway. elsin@rr-research.no., Wälchli S; Translational Research Unit, Department of Cellular Therapy, Oslo University Hospital, Oslo, Norway. sebastw@rr-research.no.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Jun 08; Vol. 14 (1), pp. 3375. Date of Electronic Publication: 2023 Jun 08.
DOI: 10.1038/s41467-023-39097-x
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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