EnglishChimeric antigen receptor (CAR)-expressing T cells are a promising therapeutic option for patients with cancer. We developed a new CAR directed against the disialoganglioside GD2, a surface molecule expressed in neuroblastoma and in other neuroectoderm-derived neoplasms. The anti-GD2 single-chain variable fragment (scFv) derived from a murine antibody of IgM class was linked, via a human CD8α hinge-transmembrane domain, to the signaling domains of the costimulatory molecules 4-1BB (CD137) and CD3-ζ. The receptor was expressed in T lymphocytes by retroviral transduction and anti-tumor activities were assessed by targeting GD2-positive neuroblastoma cells using in vitro cytotoxicity assays and a xenograft model. Transduced T cells expressed high levels of anti-GD2 CAR and exerted a robust and specific anti-tumor activity in 4- and 48-hour cultures with neuroblastoma cells. Cytotoxicity was associated with the release of pro-apoptotic molecules such as TRAIL and IFN-γ. These results were confirmed in a xenograft model, where anti-GD2 CAR T cells infiltrating tumors and persisting into blood circulation induced massive apoptosis of neuroblastoma cells and completely abrogated tumor growth. This anti-GD2 CAR represents a powerful new tool to redirect T cells against GD2. The preclinical results of this study warrant clinical testing of this approach in neuroblastoma and other GD2-positive malignancies.
| Data di pubblicazione: | 2015 |
| Titolo: | A novel anti-GD2/4-1BB chimeric antigen receptor triggers neuroblastoma cell killing |
| Autore/i: | Prapa, Malvina; Caldrer, Sara; Spano, Maria Carlotta; Bestagno, Marco; Golinelli, Giulia; Grisendi, Giulia; Petrachi, Tiziana; Conte, Pierfranco; Horwitz, Edwin M.; Campana, Dario; Paolucci, Paolo; Dominici, Massimo |
| Autore/i UNIMORE: | |
| Digital Object Identifier (DOI): | 10.18632/oncotarget.4670 |
| Rivista: | |
| Volume: | 6 |
| Fascicolo: | 28 |
| Pagina iniziale: | 24884 |
| Pagina finale: | 24894 |
| Codice identificativo ISI: | WOS:000363160100029 |
| Codice identificativo Scopus: | 2-s2.0-84944463280 |
| Codice identificativo Pubmed: | 26298772 |
| Citazione: | A novel anti-GD2/4-1BB chimeric antigen receptor triggers neuroblastoma cell killing / Prapa, Malvina; Caldrer, Sara; Spano, Maria Carlotta; Bestagno, Marco; Golinelli, Giulia; Grisendi, Giulia; Petrachi, Tiziana; Conte, Pierfranco; Horwitz, Edwin M.; Campana, Dario; Paolucci, Paolo; Dominici, Massimo. - In: ONCOTARGET. - ISSN 1949-2553. - 6:28(2015), pp. 24884-24894. |
| Tipologia | Articolo su rivista |
File in questo prodotto:
| File | Descrizione | Tipologia | |
|---|---|---|---|
| Prapa M et al. Oncotarget 2015.pdf | Versione editoriale | Open Access Visualizza/Apri |
I documenti presenti in Iris Unimore sono rilasciati con licenza Creative Commons Attribuzione - Non commerciale - Non opere derivate 3.0 Italia, salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris
Copyright © 2019