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Life sciences · Journal article
Cell Death and Disease · November 3, 2026
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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.