Alectinib boosts anti-tumor efficacy of disialoganglioside 2 chimeric antigen receptor T cells in ALK-mutated neuroblastoma by suppressing programmed death-ligand 1.
1/5 보강
[BACKGROUND] High-risk ALK-mutant neuroblastoma (NB) presents challenges due to drug resistance and an immunosuppressive tumour microenvironment (TME).
APA
Sugitatsu Y, Tomida A, et al. (2026). Alectinib boosts anti-tumor efficacy of disialoganglioside 2 chimeric antigen receptor T cells in ALK-mutated neuroblastoma by suppressing programmed death-ligand 1.. British journal of cancer. https://doi.org/10.1038/s41416-026-03363-8
MLA
Sugitatsu Y, et al.. "Alectinib boosts anti-tumor efficacy of disialoganglioside 2 chimeric antigen receptor T cells in ALK-mutated neuroblastoma by suppressing programmed death-ligand 1.." British journal of cancer, 2026.
PMID
41866626 ↗
Abstract 한글 요약
[BACKGROUND] High-risk ALK-mutant neuroblastoma (NB) presents challenges due to drug resistance and an immunosuppressive tumour microenvironment (TME). Combining molecular targeted therapy with adoptive cell therapy offers a potential therapeutic strategy.
[OBJECTIVE] To investigate the effects of alectinib, an ALK inhibitor, with disialoganglioside 2 (GD2) chimeric antigen receptor T (CAR-T) cell therapy in overcoming immune evasion in ALK-mutant NB.
[METHODS] Interferon gamma-induced programmed death-ligand 1 (PD-L1) expression and ALK signalling were analysed in ALK-mutant NB cells. The combination of alectinib and GD2 CAR-T cells was assessed in vitro, including sequential co-culture assays, and in vivo in an ALK-mutant xenograft model with multiple treatment arms.
[RESULTS] Alectinib suppressed PD-L1 expression by inhibiting ALK downstream pathways, including STAT3 and ERK1/2 phosphorylation. In vitro studies showed enhanced anti-tumour efficacy of GD2 CAR-T cells in combination with alectinib, with synergistic effect becoming evident in sequential coculture models. In vivo, the combination therapy reduced tumour growth, extended survival, and was associated with decreased PD-L1 expression and increased CAR-T cell infiltration.
[CONCLUSION] Alectinib enhances the efficacy of GD2 CAR-T therapy in ALK-mutant NB primarily by attenuating PD-L1-mediated immune evasion, supporting its potential as a combinatorial therapeutic strategy.
[OBJECTIVE] To investigate the effects of alectinib, an ALK inhibitor, with disialoganglioside 2 (GD2) chimeric antigen receptor T (CAR-T) cell therapy in overcoming immune evasion in ALK-mutant NB.
[METHODS] Interferon gamma-induced programmed death-ligand 1 (PD-L1) expression and ALK signalling were analysed in ALK-mutant NB cells. The combination of alectinib and GD2 CAR-T cells was assessed in vitro, including sequential co-culture assays, and in vivo in an ALK-mutant xenograft model with multiple treatment arms.
[RESULTS] Alectinib suppressed PD-L1 expression by inhibiting ALK downstream pathways, including STAT3 and ERK1/2 phosphorylation. In vitro studies showed enhanced anti-tumour efficacy of GD2 CAR-T cells in combination with alectinib, with synergistic effect becoming evident in sequential coculture models. In vivo, the combination therapy reduced tumour growth, extended survival, and was associated with decreased PD-L1 expression and increased CAR-T cell infiltration.
[CONCLUSION] Alectinib enhances the efficacy of GD2 CAR-T therapy in ALK-mutant NB primarily by attenuating PD-L1-mediated immune evasion, supporting its potential as a combinatorial therapeutic strategy.