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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
Nature communications, 06/2023, Letnik: 14, Številka: 1Journal Article
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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Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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