Dual Bcl-2/Bcl-xl inhibition via AZD0466 combines with immune checkpoint blockade to enhance anti-tumour activity
Abstract
Small molecule inhibitors designed to specifically target oncogenic proteins have demonstrated potent anti-tumour activities due to direct effects on tumour cells survival and/or proliferation. However, the effects of these compounds on normal cells, specifically immune cells and their potential to impede or enhance anti-cancer immunotherapies has yet to be fully explored. Using an in vitro co-culture system to assess CD8+ T cell killing of tumour cells, we identified compounds that inhibit Bcl-2 and Bcl-xl as agents that can induce tumour cell death without impacting the differentiation or function of anti-tumour T cells. Accordingly, in vivo treatment of mice bearing solid tumours with a combination of the Bcl-2/Bcl-xl inhibitor AZD0466 and anti-PD-L1 immunotherapy resulted in enhanced anti-tumour effects and improved survival compared to equivalent monotherapies.
Fields of Study & Subjects
Cancer Immunotherapy and Biomarkers
CAR-T cell therapy research
Phagocytosis and Immune Regulation
Publication details
- Journal / source
- Cell Death and Disease
- Publisher
- Springer Science and Business Media LLC
- Volume
- 17
- Issue
- 1
- Pages
- 177–177
- Publication date
- 6 January 2026
- Language
- EN