ArticleInternational journal of cancer2010
Effect of a small molecule BCL-2 inhibitor on immune function and use with a recombinant vaccine.
Article in International journal of cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
- Regulatory T cells in solid tumor immunotherapy: effect, mechanism and clinical application.Cell death & disease · 2025Review
- 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
- Cellular and humoral immune response to mRNA COVID-19 vaccination in subjects with chronic lymphocytic leukemia.Blood advances · 2022Article
- Review
- Therapy of Established Tumors with Rationally Designed Multiple Agents Targeting Diverse Immune-Tumor Interactions: Engage, Expand, Enable.Cancer immunology research · 2021Article
- Semaphorin4D Inhibition Improves Response to Immune-Checkpoint Blockade via Attenuation of MDSC Recruitment and Function.Cancer immunology research · 2019Article
- Bcl-2 Inhibition to Overcome Resistance to Chemo- and Immunotherapy.International journal of molecular sciences · 2018Review
- BH3 mimetics induce apoptosis independent of DRP-1 in melanoma.Cell death & disease · 2018Article
- Killing Two Cells with One Stone: Pharmacologic BCL-2 Family Targeting for Cancer Cell Death and Immune Modulation.Frontiers in pediatrics · 2016Review
- Dual effects of a targeted small-molecule inhibitor (cabozantinib) on immune-mediated killing of tumor cells and immune tumor microenvironment permissiveness when combined with a cancer vaccine.Journal of translational medicine · 2014Article
- 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.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Therapeutic cancer vaccines.Advances in cancer research · 2014Review
- Therapeutic cancer vaccines: past, present, and future.Advances in cancer research · 2013Review
- Targeting the Bcl-2 family for cancer therapy.Expert opinion on therapeutic targets · 2013Review
- Strategies for optimizing the clinical impact of immunotherapeutic agents such as sipuleucel-T in prostate cancer.Journal of the National Comprehensive Cancer Network : JNCCN · 2012Article
- Therapeutic cancer vaccines: the latest advancement in targeted therapy.American journal of therapeutics · 2012Review
- The tipping point for combination therapy: cancer vaccines with radiation, chemotherapy, or targeted small molecule inhibitors.Seminars in oncology · 2012Review
- Distinct effects of saracatinib on memory CD8+ T cell differentiation.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- Therapeutic cancer vaccines: current status and moving forward.Journal of the National Cancer Institute · 2012Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Small molecule BCL-2 inhibitors are being examined as monotherapy in phase I/II clinical trials for several types of tumors. However, few data are available about the effect of BCL-2 inhibitors on immune function. The aims of our study were to investigate the effect of a small molecule BCL-2 inhibitor on immune function and determine the most effective way of combining this inhibitor with a recombinant vaccine to treat tumors. The in vitro effect of the pan-BCL-2 inhibitor GX15-070 was assessed in mouse CD8 T lymphocytes at 2 different stages of activation as well as regulatory T lymphocytes (Treg). The in vivo effect of GX15-070 after recombinant vaccinia/fowlpox CEA-TRICOM vaccination was analyzed in tumor-infiltrating lymphocytes, and in splenocytes of mice bearing subcutaneous tumors. The therapeutic efficacy of such sequential therapy was measured as a reduction of pulmonary tumor nodules. Activated mature CD8 T lymphocytes were more resistant to GX15-070 as compared to early-activated cells. Treg function was significantly decreased after treatment with the BCL-2 inhibitor. In vivo, GX15-070 was given after vaccination so as to not negatively impact the induction of vaccine-mediated immunity, resulting in increased intratumoral activated CD8:Treg ratio and significant reduction of pulmonary tumor nodules. Our study is the first to show the effect of a small molecule BCL-2 inhibitor on the immune system and following a vaccine. It is also the first to demonstrate the efficacy of this sequence in reducing tumors in mouse models, providing a rationale for the design of combinational clinical studies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.