Elraglusib (9-ING-41), a selective small-molecule inhibitor of glycogen synthase kinase-3 beta, reduces expression of immune checkpoint molecules PD-1, TIGIT and LAG-3 and enhances CD8⁺ T cell cytolytic killing of melanoma cells.

ABSTRACT:

Background

Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase with multiple roles in tumour growth, cell invasion and metastasis. We have previously established GSK-3 as an upstream regulator of PD-1 gene expression in CD8 + T cells and demonstrated that GSK-3 inhibition is as effective as anti-PD-1 mAb blockade in controlling tumour growth. Elraglusib (9-ING-41) is a specific small-molecule inhibitor of GSK-3β with clinical activity in patients with advanced cancers, including a patient with refractory melanoma whose response provided the rationale for the current study.

Methods

The B16 melanoma mouse model was used to observe the effect of elraglusib on tumour growth either as a single agent or in combination (simultaneously and sequentially) with anti-PD-1 mA

SUBMITTER: Shaw G 

PROVIDER: S-EPMC9472445 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature