ArticleOncotarget2019
Targeted enhancement of the therapeutic window of L19-TNF by transient and selective inhibition of RIPK1-signaling cascade.
Article in Oncotarget, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 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
9 citing papers in PubMed, 13 citations in OpenAlex.
- Molecular imaging supports the development of multispecific cancer antibodies.Nature reviews. Clinical oncology · 2024Review
- A novel strategy to generate immunocytokines with activity-on-demand using small molecule inhibitors.EMBO molecular medicine · 2024Article
- Immunocytokines with activity-on-demand by combination with small molecule inhibitors.EMBO molecular medicine · 2024Article
- Tumor-Homing Antibody-Cytokine Fusions for Cancer Therapy.OncoTargets and therapy · 2024Review
- The emergence of AntibodyPlus: the future trend of antibody-based therapeutics.Antibody therapeutics · 2022Review
- The present and future of immunocytokines for cancer treatment.Cellular and molecular life sciences : CMLS · 2022Review
- Enhanced Detection of Desmoplasia by Targeted Delivery of Iron Oxide Nanoparticles to the Tumour-Specific Extracellular Matrix.Pharmaceutics · 2021Article
- An Attenuated Targeted-TNF Localizes to Tumors In Vivo and Regains Activity at the Site of Disease.International journal of molecular sciences · 2021Article
- Utilizing Immunocytokines for Cancer Therapy.Antibodies (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionCytokine-based products are gaining importance for cancer immunotherapy. L19-TNF is a clinical-stage antibody-cytokine fusion protein that selectively accumulates to tumors and displays potent anticancer activity in preclinical models. Here, we describe an innovative approach to transiently inhibit off-target toxicity of L19-TNF, while maintaining antitumor activity.
methodsGSK'963, a potent small molecule inhibitor of RIPK1, was tested in tumor-bearing mice for its ability to reduce acute toxicity associated with TNF signaling. The biological effects of L19-TNF on tumor cells, lymphocytes and tumor vessels were investigated with the aim to enable the administration of TNF doses, which would otherwise be lethal.
resultsTransient inhibition of RIPK1 allowed to increase the maximal tolerated dose of L19-TNF. The protective effect of GSK'963 did not affect the selective localization of the immunocytokine to tumors as evidenced by quantitative biodistribution analysis and allowed to reach high local TNF concentrations around tumor blood vessels, causing diffused vascular shutdown and hemorrhagic necrosis within the neoplastic mass.
conclusionsThe selective inhibition of RIPK1 with small molecule inhibitors can be used as a pharmaceutical tool to transiently mask TNF activity and improve the therapeutic window of TNF-based biopharmaceuticals. Similar approaches may be applicable to other pro-inflammatory cytokines.
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