ArticleLeukemia2011
The novel antisense Bcl-2 inhibitor SPC2996 causes rapid leukemic cell clearance and immune activation in chronic lymphocytic leukemia.
Article in Leukemia, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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.
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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
24 citing papers in PubMed, 47 citations in OpenAlex.
- Advancing cancer treatments: The role of oligonucleotide-based therapies in driving progress.Molecular therapy. Nucleic acids · 2024Review
- A Comprehensive Review of Small Interfering RNAs (siRNAs): Mechanism, Therapeutic Targets, and Delivery Strategies for Cancer Therapy.International journal of nanomedicine · 2023Review
- Making Sense of Antisense Oligonucleotide Therapeutics Targeting Bcl-2.Pharmaceutics · 2022Review
- Recent Advances in Oligonucleotide Therapeutics in Oncology.International journal of molecular sciences · 2021Review
- Emerging role of long non-coding RNAs in cancer chemoresistance: unravelling the multifaceted role and prospective therapeutic targeting.Molecular biology reports · 2020Review
- Review
- Review
- Role of Non-Coding RNAs in the Development of Targeted Therapy and Immunotherapy Approaches for Chronic Lymphocytic Leukemia.Journal of clinical medicine · 2020Review
- CpG stimulation of chronic lymphocytic leukemia cells induces a polarized cell shape and promotes migration in vitro and in vivo.PloS one · 2020Article
- Exploiting Mitochondrial Vulnerabilities to Trigger Apoptosis Selectively in Cancer Cells.Cancers · 2019Review
- Antisense-mediated splice intervention to treat human disease: the odyssey continues.F1000Research · 2019Review
- Non-coding RNAs: the riddle of the transcriptome and their perspectives in cancer.Annals of translational medicine · 2018Review
- Long Noncoding RNA in Cancer: Wiring Signaling Circuitry.Trends in cell biology · 2018Review
- Targeting the Bcl-2 Family in B Cell Lymphoma.Frontiers in oncology · 2018Review
- From the Cover: The Minipig is a Suitable Non-Rodent Model in the Safety Assessment of Single Stranded Oligonucleotides.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
- Hepatotoxicity of high affinity gapmer antisense oligonucleotides is mediated by RNase H1 dependent promiscuous reduction of very long pre-mRNA transcripts.Nucleic acids research · 2016Article
- Broad targeting of resistance to apoptosis in cancer.Seminars in cancer biology · 2015Review
- Co-targeting of Bcl-2 and mTOR pathway triggers synergistic apoptosis in BH3 mimetics resistant acute lymphoblastic leukemia.Oncotarget · 2015Article
- Grand challenges in biomaterials.Frontiers in bioengineering and biotechnology · 2014Article
- Aurora kinases in childhood acute leukemia: the promise of aurora B as therapeutic target.Leukemia · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SPC2996 is a novel locked nucleic acid phosphorothioate antisense molecule targeting the mRNA of the Bcl-2 oncoprotein. We investigated the mechanism of action of SPC2996 and the basis for its clinically observed immunostimulatory effects in chronic lymphocytic leukemia (CLL). Patients with relapsed CLL were treated with a maximum of six doses of SPC2996 (0.2-6 mg/kg) in a multicenter phase I trial. Microarray-based transcriptional profiling of circulating CLL cells was carried out before and after the first infusion of SPC2996 in 18 patients. Statistically significant transcriptomic changes were observed at doses 4 mg/kg and occurred as early as 24 h after the first infusion of the oligonucleotide. SPC2996 induced the upregulation of 466 genes including a large number of immune response and apoptotic regulator molecules, which were enriched for Toll-like receptor response genes. Serum measurements confirmed the release of pro-inflammatory cytokines including chemokine (C-C motif) ligand 3 (macrophage inflammatory protein 1α) and tumor necrosis factor-α, thereby validating the in vivo transcriptomic data at the protein level. SPC2996 caused a 50% reduction of circulating lymphocytes in five of 18 (28%) patients, which was found to be independent of its immunostimulatory and anti-Bcl-2 effects.
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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.