ArticlePloS one2012
Adoptive transfer of siRNA Cblb-silenced CD8+ T lymphocytes augments tumor vaccine efficacy in a B16 melanoma model.
Article in PloS one, 2012. 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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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
29 citing papers in PubMed.
- Development and validation of a prognostic model based on T cell signature genes in colon cancer using single-cell RNA sequencing.Clinical and experimental medicine · 2026Article
- Mechanisms of Cbl-Mediated Ubiquitination of Proteins in T and Natural Killer Cells and Effects on Immune Cell Functions.Life (Basel, Switzerland) · 2024Review
- The role of CBL family ubiquitin ligases in cancer progression and therapeutic strategies.Frontiers in pharmacology · 2024Review
- High-Performance Multi-Dynamic Bond Cross-Linked Hydrogel with Spatiotemporal siRNA Delivery for Gene-Cell Combination Therapy of Intervertebral Disc Degeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Targeting Cbl-b in cancer immunotherapy.Journal for immunotherapy of cancer · 2023Review
- The expanding role for small molecules in immuno-oncology.Nature reviews. Drug discovery · 2022Review
- Polymer-Based Constructs for Flexor Tendon Repair: A Review.Polymers · 2022Review
- Ubiquitination in T-Cell Activation and Checkpoint Inhibition: New Avenues for Targeted Cancer Immunotherapy.International journal of molecular sciences · 2021Review
- Combination of CRISPR/Cas9 System and CAR-T Cell Therapy: A New Era for Refractory and Relapsed Hematological Malignancies.Current medical science · 2021Review
- E3 ubiquitin ligase Casitas B lineage lymphoma-b and its potential therapeutic implications for immunotherapy.Clinical and experimental immunology · 2021Review
- Precision Tools in Immuno-Oncology: Synthetic Gene Circuits for Cancer Immunotherapy.Vaccines · 2020Review
- Manipulating the TCR signaling network for cellular immunotherapy: Challenges & opportunities.Molecular immunology · 2020Review
- Engineering bionic T cells: signal 1, signal 2, signal 3, reprogramming and the removal of inhibitory mechanisms.Cellular & molecular immunology · 2020Review
- E3 Ubiquitin Ligases as Immunotherapeutic Target in Atherosclerotic Cardiovascular Disease.Frontiers in cardiovascular medicine · 2020Review
- Clonal expansion of CAR T cells harboring lentivector integration in the CBL gene following anti-CD22 CAR T-cell therapy.Blood advances · 2019Article
- Gene editing: Towards the third generation of adoptive T-cell transfer therapies.Immuno-oncology technology · 2019Review
- Review
- Gene Silencing via PDA/ERK2-siRNA-Mediated Electrospun Fibers for Peritendinous Antiadhesion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2019Article
- Genome-wide CRISPR Screens in Primary Human T Cells Reveal Key Regulators of Immune Function.Cell · 2018Article
- IFT20 modulates ciliary PDGFRα signaling by regulating the stability of Cbl E3 ubiquitin ligases.The Journal of cell biology · 2018Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
The ubiquitin ligase Cbl-b is an established regulator of T cell immune response thresholds. We recently showed that adoptive cell transfer (ACT) of cblb(-/-) CD8(+) T cells enhances dendritic cell (DC) immunization-mediated anti-tumor effects in immune-competent recipients. However, translation of cblb targeting to clinically applicable concepts requires that inhibition of cblb activity be transient and reversible. Here we provide experimental evidence that inhibition of cblb using chemically synthesized siRNA has such potential. Silencing cblb expression by ex vivo siRNA transfection of polyclonal CD8(+) T cells prior to ACT increased T cell tumor infiltration, significantly delayed tumor outgrowth, and increased survival rates of tumor-bearing mice. As shown by ex vivo recall assays, cblb silencing resulted in significant augmentation of intratumoral T cell cytokine response. ACT of cblb-silenced polyclonal CD8(+) T cells combined with DC-based tumor vaccines predominantly mediated anti-tumor immune responses, whereas no signs of autoimmunity could be detected. Importantly, CBLB silencing in human CD8(+) T cells mirrored the effects observed for cblb-silenced and cblb-deficient murine T cells. Our data validate the concept of enhanced anti-tumor immunity by repetitive ACT of ex vivo cblb siRNA-silenced hyper-reactive CD8(+) T cells as add-on adjuvant therapy to augment the efficacy of existing cancer immunotherapy regimens in clinical practice.
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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.