ArticleJournal of virology2008
Targeting the apoptotic pathway with BCL-2 inhibitors sensitizes primary chronic lymphocytic leukemia cells to vesicular stomatitis virus-induced oncolysis.
Article in Journal of virology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 46 citations in OpenAlex.
- Apoptotic modulators enhance oncolytic virus-induced cytokine killing in acute myeloid leukaemia (AML).British journal of cancer · 2026Article
- Cancer-Specific Activation of the Vesicular Stomatitis Virus Matrix by Survivin Promoter in Breast Cancer Cells.Molecular biotechnology · 2026Article
- Therapeutic potential of oncolytic viruses in hematopoietic malignancies: from preclinical insights to clinical realities.Frontiers in microbiology · 2026Review
- FGL2 promotes tumour growth and attenuates infiltration of activated immune cells in melanoma and ovarian cancer models.Scientific reports · 2024Article
- Review
- Oncolytic Viruses and Hematological Malignancies: A New Class of Immunotherapy Drugs.Current oncology (Toronto, Ont.) · 2020Review
- The Oncolytic Virotherapy Era in Cancer Management: Prospects of Applying H-1 Parvovirus to Treat Blood and Solid Cancers.Frontiers in oncology · 2017Article
- Targeting Melanoma with Cancer-Killing Viruses.The open virology journal · 2017Article
- Oncolytic reovirus enhances rituximab-mediated antibody-dependent cellular cytotoxicity against chronic lymphocytic leukaemia.Leukemia · 2015Article
- Intratumoral oncolytic adenoviral treatment modulates the glioma microenvironment and facilitates systemic tumor-antigen-specific T cell therapy.Oncoimmunology · 2015Article
- Article
- Oncolytic activity of avian influenza virus in human pancreatic ductal adenocarcinoma cell lines.Journal of virology · 2014Article
- Triptolide-mediated inhibition of interferon signaling enhances vesicular stomatitis virus-based oncolysis.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Article
- Oncolytic vesicular stomatitis virus in an immunocompetent model of MUC1-positive or MUC1-null pancreatic ductal adenocarcinoma.Journal of virology · 2013Article
- BCL-2 inhibitors sensitize therapy-resistant chronic lymphocytic leukemia cells to VSV oncolysis.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Article
- Targeting and killing of metastatic cells in the transgenic adenocarcinoma of mouse prostate model with vesicular stomatitis virus.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Article
- Systems analysis of a RIG-I agonist inducing broad spectrum inhibition of virus infectivity.PLoS pathogens · 2013Article
- Vesicular stomatitis virus as a flexible platform for oncolytic virotherapy against cancer.The Journal of general virology · 2012Review
- Enhancing VSV oncolytic activity with an improved cytosine deaminase suicide gene strategy.Cancer gene therapy · 2011Article
- Oncolytic vesicular stomatitis virus induces apoptosis in U87 glioblastoma cells by a type II death receptor mechanism and induces cell death and tumor clearance in vivo.Journal of virology · 2011Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Chronic lymphocytic leukemia (CLL) is characterized by clonal accumulation of CD5(+) CD19(+) B lymphocytes that are arrested in the G(0)/G(1) phase of the cell cycle and fail to undergo apoptosis because of overexpression of the antiapoptotic B-cell CLL/lymphoma 2 (BCL-2) protein. Oncolytic viruses, such as vesicular stomatitis virus (VSV), have emerged as potential anticancer agents that selectively target and kill malignant cells via the intrinsic mitochondrial pathway. Although primary CLL cells are largely resistant to VSV oncolysis, we postulated that targeting the apoptotic pathway via inhibition of BCL-2 may sensitize CLL cells to VSV oncolysis. In the present study, we examined the capacity of EM20-25--a small-molecule antagonist of the BCL-2 protein--to overcome CLL resistance to VSV oncolysis. We demonstrate a synergistic effect of the two agents in primary ex vivo CLL cells (combination index of 0.5; P < 0.0001). In a direct comparison of peripheral blood mononuclear cells from healthy volunteers with primary CLL, the two agents combined showed a therapeutic index of 19-fold; furthermore, the combination of VSV and EM20-25 increased apoptotic cell death in Karpas-422 and Granta-519 B-lymphoma cell lines (P < 0.005) via the intrinsic mitochondrial pathway. Mechanistically, EM20-25 blocked the ability of the BCL-2 protein to dimerize with proapoptotic BAX protein, thus sensitizing CLL to VSV oncolytic stress. Together, these data indicate that the use of BCL-2 inhibitors may improve VSV oncolysis in treatment-resistant hematological malignancies, such as CLL, with characterized defects in the apoptotic response.
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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.