Anti-GD2 CAR T cells efficiently target Ewing’s sarcoma

Abstract Ewing’s sarcoma (ES) is an aggressive cancer primarily affecting children and young adults. Although chimeric antigen receptor (CAR) T cell therapy has achieved remarkable success in hematologic malignancies, its efficacy against solid tumors such as ES remains limited. Our previous studies demonstrated the therapeutic potential of GD2 CAR T cells against brain tumors and showed that a truncated GD2 CAR enhances the tumor-targeting ability and antitumor efficacy of mesenchymal stromal/stem cells against metastatic ES. Here, we further investigated the therapeutic potential of GD2 CAR T cells in ES, a disease for which effective treatment options remain a significant unmet medical need. The antitumor activity of GD2 CAR T cells was assessed using different two-dimensional and three-dimensional in vitro ES models and an in vivo ES xenograft model. GD2 CAR T cells effectively killed ES cells in both two-dimensional and three-dimensional settings, including an ES cell line displaying low GD2 expression. In vivo, GD2 CAR T cells efficiently targeted localized ES tumors and counteracted tumor growth. CAR T cells infiltrated the tumors and were also detected in the spleen of treated mice. Overall, these findings support the efficacy of GD2 CAR T cells against both in vitro models and a localized in vivo model of ES. These findings underscore the potential of GD2 CAR T cell-based therapies to improve treatment outcomes in ES and other lethal GD2-positive malignancies.

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Publication Details

Journal
Cell Death and Disease
Published
2026-11-03
DOI
https://doi.org/10.1038/s41419-026-09268-x
Primary Topic
CAR-T cell therapy research
Type
article
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article

Anti-GD2 CAR T cells efficiently target Ewing’s sarcoma

Giovanni Neri, Giulia Golinelli, Federico Banchelli, Marco Bestagno et al.
Cell Death and Disease
CAR-T cell therapy research
article

Anti-GD2 CAR T cells efficiently target Ewing’s sarcoma

Giovanni Neri, Giulia Golinelli, Federico Banchelli, Marco Bestagno, Giulia Rovesti, Jonathan Vinet, Malvina Prapa, Bruce L. Levine, Maria Cristina Baschieri, Massimo Dominici, Riccardo Cuoghi Costantini, Rosanna Di Tinco, Carlotta Spano, Marco Silingardi, Edwin M. Horwitz, Tiziana Petrachi, Laura Bertoni, Chiara Chiavelli, Giuseppe Pugliese, Giovanni Palazzi, Alice Morellini, Leonardo Brini
article en

Abstract

Abstract Ewing’s sarcoma (ES) is an aggressive cancer primarily affecting children and young adults. Although chimeric antigen receptor (CAR) T cell therapy has achieved remarkable success in hematologic malignancies, its efficacy against solid tumors such as ES remains limited. Our previous studies demonstrated the therapeutic potential of GD2 CAR T cells against brain tumors and showed that a truncated GD2 CAR enhances the tumor-targeting ability and antitumor efficacy of mesenchymal stromal/stem cells against metastatic ES. Here, we further investigated the therapeutic potential of GD2 CAR T cells in ES, a disease for which effective treatment options remain a significant unmet medical need. The antitumor activity of GD2 CAR T cells was assessed using different two-dimensional and three-dimensional in vitro ES models and an in vivo ES xenograft model. GD2 CAR T cells effectively killed ES cells in both two-dimensional and three-dimensional settings, including an ES cell line displaying low GD2 expression. In vivo, GD2 CAR T cells efficiently targeted localized ES tumors and counteracted tumor growth. CAR T cells infiltrated the tumors and were also detected in the spleen of treated mice. Overall, these findings support the efficacy of GD2 CAR T cells against both in vitro models and a localized in vivo model of ES. These findings underscore the potential of GD2 CAR T cell-based therapies to improve treatment outcomes in ES and other lethal GD2-positive malignancies.

Cell Death and Disease
University of Modena and Reggio Emilia (IT), Emory University (US), Azienda Ospedaliero-Universitaria di Modena (IT), Albanian University (AL), CellPly S.r.l. (Italy) (IT), University of Pennsylvania (US), International Centre for Genetic Engineering and Biotechnology (IT)
Openalex Percentile: Top 17%
CAR-T cell therapy research
DOIOpen Access PDFOpenAlex
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