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Radiopharmaceuticals enhance CAR T-cells against radio-sensitive and radio-resistant neuroblastoma by tumor sensitization and TME remodeling [scRNA-Seq]

GSE330930 Homo sapiens Expression profiling by high throughput sequencing 8 samples Submitted 2026/05/18 Platform GPL34284
Summary
Chimeric antigen receptor (CAR) T-cell therapy has limited efficacy against solid tumors such as neuroblastoma (NB). Key obstacles include extensive tumor burden and the presence of an immunosuppressive tumor microenvironment (TME). We employ targeted radiopharmaceutical therapy (RPT) using [67Cu]Cu-LLP2A and find that it potentiated the anti-tumor activity of CAR T-cells in radio-sensitive and radio-resistant NB models via distinct mechanisms. In radio-sensitive NB, RPT is directly tumoricidal while also enhancing CAR T-cell efficacy through pro-immune pathways, most notably via the TNFα pathway, leading to paracrine activation of T-cells. In radio-resistant NB, RPT improves CAR T-cells by remodeling the myeloid compartment in the TME and increasing the formation of immunological niches of cytotoxic CD8⁺ GZMB⁺ and CD4⁺ GZMB+ CAR T-cells. While neither treatment modality alone can effectively treat NB, the combination of VLA-4-targeted RPT and GD2 or B7-H3 CAR T-cells augments anti-tumor efficacy, resulting in marked tumor regression in preclinical NB models.
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Also filed as BioProject PRJNA1466209 and SRA study SRP700508. Searching any of these in the dataset finder brings you back here.

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