ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Pan-Bcl-2 inhibitor, GX15-070 (obatoclax), decreases human T regulatory lymphocytes while preserving effector T lymphocytes: a rationale for its use in combination immunotherapy.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 30 citations in OpenAlex.
- Regulatory T cells in solid tumor immunotherapy: effect, mechanism and clinical application.Cell death & disease · 2025Review
- Integrated stress response (ISR) activation and apoptosis through HRI kinase by PG3 and other p53 pathway-restoring cancer therapeutics.Oncotarget · 2024Article
- MCL1 inhibition targets Myeloid Derived Suppressors Cells, promotes antitumor immunity and enhances the efficacy of immune checkpoint blockade.Cell death & disease · 2024Article
- Small-Molecule PROTACs for Cancer Immunotherapy.Molecules (Basel, Switzerland) · 2022Review
- Efficacy evaluation of multi-immunotherapy in ovarian cancer: From bench to bed.Frontiers in immunology · 2022Review
- RedH and PigC Catalyze the Biosynthesis of Hybrubins via Phosphorylation of 4'-Methoxy-2,2'-Bipyrrole-5'-Carbaldehyde.Applied and environmental microbiology · 2020Article
- Manipulation of the immune system by non-small cell lung cancer and possible therapeutic interference.Cancer drug resistance (Alhambra, Calif.) · 2020Review
- BH3 mimetics induce apoptosis independent of DRP-1 in melanoma.Cell death & disease · 2018Article
- Immune cell landscape in therapy-naïve squamous cell and adenocarcinomas of the lung.Virchows Archiv : an international journal of pathology · 2018Article
- Article
- Low-dose interleukin-2 promotes STAT-5 phosphorylation, TClinical and experimental immunology · 2017Article
- Killing Two Cells with One Stone: Pharmacologic BCL-2 Family Targeting for Cancer Cell Death and Immune Modulation.Frontiers in pediatrics · 2016Review
- Obatoclax regulates the proliferation and fusion of osteoclast precursors through the inhibition of ERK activation by RANKL.Molecules and cells · 2015Article
- Potential utility of the pan-Bcl-2 inhibitor GX15-070 (obatoclax) in cancer immunotherapy.OncoimmunologyArticle
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Bcl-2 inhibitors are currently being evaluated in clinical studies for treatment of patients with solid tumors and hematopoietic malignancies. In this study we explored the potential for combining the pan-Bcl-2 inhibitor GX15-070 (GX15; obatoclax) with immunotherapeutic modalities. We evaluated the in vitro effects of GX15 on human T cell subsets obtained from PBMCs in terms of activation, memory, and suppressive function. Our results indicated that in healthy-donor PBMCs, mature-activated T cells were more resistant to GX15 than early-activated T cells, and that GX15 preserved memory but not non-memory T cell populations. Furthermore, GX15 increased the apoptosis of regulatory T cells (Tregs), profoundly downregulated FOXP3 and CTLA-4 in a dose-dependent manner, and decreased their suppressive function. Treating PBMCs obtained from ovarian cancer patients with GX15 also resulted in increased CD8(+):Treg and CD4(+):Treg ratios. These results support preclinical studies in which mice vaccinated before treatment with GX15 showed the greatest reduction in metastatic lung tumors as a result of increased apoptotic resistance of mature CD8(+) T cells and decreased Treg function brought about by GX15. Taken together, these findings suggest that when a Bcl-2 inhibitor is combined with active immunotherapy in humans, such as the use of a vaccine or immune checkpoint inhibitor, immunotherapy should precede administration of the Bcl-2 inhibitor to allow T cells to become mature, and thus resistant to the cytotoxic effects of the Bcl-2 inhibitor.
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Registered trials
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