Dual Bcl-2/Bcl-xl inhibition via AZD0466 combines with immune checkpoint blockade to enhance anti-tumour activity
- Author(s)
- Newman, DM; Andersen, CL; Cluse, LA; Newbold, A; Fraser, P; Legg, BWC; Xu, LK; Mele, DA; Johnstone, RW;
- Details
- Publication Year 2026-01-06,Volume 17,Issue #1,Page 177
- Journal Title
- Cell Death & Disease
- Publication Type
- Research article
- 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.
- Publisher
- Springer Nature
- Keywords
- Animals; *bcl-X Protein/antagonists & inhibitors/metabolism; Mice; Humans; *Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors/metabolism; *Immune Checkpoint Inhibitors/pharmacology/therapeutic use; Cell Line, Tumor; *Aniline Compounds/pharmacology; CD8-Positive T-Lymphocytes/drug effects/immunology; Female; Mice, Inbred C57BL
- Department(s)
- Laboratory Research
- Publisher's Version
- https://doi.org/10.1038/s41419-025-08354-w
- Open Access at Publisher's Site
https://doi.org/10.1038/s41419-025-08354-w- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2026-01-23 11:58:23
Last Modified: 2026-02-26 02:13:19