ArticleThe Journal of clinical investigation2010
Abrogating Cbl-b in effector CD8(+) T cells improves the efficacy of adoptive therapy of leukemia in mice.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 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
57 citing papers in PubMed.
- Trial
- Targeting PIM2 improves antitumor immunity through promoting effector function and persistence of CD8 T cells.The Journal of clinical investigation · 2026Article
- The ubiquitin ligase KLHL6 drives resistance to CD8Nature · 2026Article
- Mechanisms of Cbl-Mediated Ubiquitination of Proteins in T and Natural Killer Cells and Effects on Immune Cell Functions.Life (Basel, Switzerland) · 2024Review
- CD28 co-stimulation: novel insights and applications in cancer immunotherapy.Nature reviews. Immunology · 2024Review
- T cell receptor therapeutics: immunological targeting of the intracellular cancer proteome.Nature reviews. Drug discovery · 2023Review
- Negative intracellular regulators of T-cell receptor (TCR) signaling as potential antitumor immunotherapy targets.Journal for immunotherapy of cancer · 2023Review
- A T cell resilience model associated with response to immunotherapy in multiple tumor types.Nature medicine · 2022Article
- Overproduction of IFNγ by Cbl-b-Deficient CD8+ T Cells Provides Resistance against Regulatory T Cells and Induces Potent Antitumor Immunity.Cancer immunology research · 2022Article
- Ubiquitination in T-Cell Activation and Checkpoint Inhibition: New Avenues for Targeted Cancer Immunotherapy.International journal of molecular sciences · 2021Review
- Engineering enhanced CAR T-cells for improved cancer therapy.Nature cancer · 2021Review
- Tumor rejection inJournal for immunotherapy of cancer · 2021Article
- E3 ubiquitin ligase Casitas B lineage lymphoma-b and its potential therapeutic implications for immunotherapy.Clinical and experimental immunology · 2021Review
- Optimized gene engineering of murine CAR-T cells reveals the beneficial effects of IL-15 coexpression.The Journal of experimental medicine · 2021Article
- Targeting ubiquitin signaling for cancer immunotherapy.Signal transduction and targeted therapy · 2021Review
- A Fas-4-1BB fusion protein converts a death to a pro-survival signal and enhances T cell therapy.The Journal of experimental medicine · 2020Article
- Precision Tools in Immuno-Oncology: Synthetic Gene Circuits for Cancer Immunotherapy.Vaccines · 2020Review
- miR-155 Overexpression in OT-1 CD8Molecular therapy oncolytics · 2020Article
- E3 Ubiquitin Ligases as Immunotherapeutic Target in Atherosclerotic Cardiovascular Disease.Frontiers in cardiovascular medicine · 2020Review
- Silica Nanocapsules with Different Sizes and Physicochemical Properties as Suitable Nanocarriers for Uptake in T-Cells.International journal of nanomedicine · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
The clinical use of adoptive immunotherapy with tumor-reactive T cells to treat established cancers is limited in part by the poor in vivo survival and function of the transferred T cells. Although administration of exogenous cytokines such as IL-2 can promote T cell survival, such strategies have many nonspecific activities and are often associated with toxicity. We show here that abrogating expression of Casitas B-lineage lymphoma b (Cbl-b), a negative regulator of lymphocyte activation, in tumor-reactive CD8(+) T cells expanded ex vivo increased the efficacy of adoptive immunotherapy of disseminated leukemia in mice. Mechanistically, Cbl-b abrogation bypassed the requirement for exogenous IL-2 administration for tumor eradication in vivo. In addition, CD8(+) T cells lacking Cbl-b demonstrated a lower threshold for activation, better survival following target recognition and stimulation, and enhanced proliferative responses as a result of both IL-2-dependent and -independent pathways. Importantly, siRNA knockdown of Cbl-b in human CD8(+)CD28- effector T cell clones similarly restored IL-2 production and proliferation following target recognition independent of exogenous IL-2, enhanced IFN-γ production, and increased target avidity. Thus, abrogating Cbl-b expression in effector T cells may improve the efficacy of adoptive therapy of some human malignancies.
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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.