GD2-Specific CAR T Cells Demonstrate Potent and Targeted Anti-Tumor Efficacy Against Melanoma and .

BACKGROUND

Disialoganglioside (GD2) is a tumor-associated antigen that is highly expressed in various neuroectodermal cancers, including melanoma. While chimeric antigen receptor (CAR) T-cell immunotherapy has demonstrated remarkable success in treating hematologic neoplasms, the identification of suitable targets remains a major obstacle in translating this approach to solid tumors.

METHODS

Peripheral blood T lymphocytes from six healthy donors were used to generate GD2-specific CAR T cells via retroviral transduction. The resulting GD2.CAR T cells were characterized by NanoString transcriptome profiling, flow cytometry with hierarchical stochastic neighbor embedding (HSNE) dimensionality reduction, and cytotoxicity assays against GD2 and GD2 melanoma cell lines. experiments were also performed using GD2 xenograft models and a single intratumoral dose of 8 × 10 GD2.CAR T cells.

RESULT

The GD2.CAR T cell population exhibited a predominantly naive phenotype (CD8CD40LCD69CD107a4-1BBFasL) and effective anti-tumor mechanisms involving the granzyme A/B axis, the Fas/FasL axis, and cytokine release. Transcriptome analysis revealed transduction-related effects on proliferation and a shift towards an effector phenotype during early co-culture with tumor cells, accompanied by upregulation of interferon-gamma (IFN-γ) and cytokine signaling genes. GD2.CAR T cells demonstrated robust cytotoxicity against GD2 melanoma cells , while significant tumor control was observed in xenograft models.

CONCLUSION

GD2.CAR T cells demonstrate potent anti-tumor activity against melanoma and , highlighting their therapeutic potential and warranting further clinical investigation.