ArticleJournal of cancer research and clinical oncology2018
Antibody-based delivery of tumor necrosis factor (L19-TNFα) and interleukin-2 (L19-IL2) to tumor-associated blood vessels has potent immunological and anticancer activity in the syngeneic J558L BALB/c myeloma model.
Article in Journal of cancer research and clinical oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 21 citations in OpenAlex.
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- The versatile electric condition in mouse embryos for genome editing using a three-step square-wave pulse electroporator.Experimental animals · 2022Article
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- Immunological Prognostic Factors in Multiple Myeloma.International journal of molecular sciences · 2021Review
- Utilizing Immunocytokines for Cancer Therapy.Antibodies (Basel, Switzerland) · 2021Review
- Bioinformatics Analysis of Hub Genes and Potential Therapeutic Agents Associated with Gastric Cancer.Cancer management and research · 2021Article
- Relationship between IL-10 and PD-L1 in esophageal carcinoma tissues and IL-10 down-regulates PD-L1 expression via Met signaling pathway.Journal of gastrointestinal oncology · 2020Article
- TRIM66 promotes malignant progression of prostate carcinoma through the JAK/STAT pathway.FEBS open bio · 2020Article
- Relationship between IL10 and PD-L1 in Liver Hepatocellular Carcinoma Tissue and Cell Lines.BioMed research international · 2020Article
- Targeted Therapy With Immunoconjugates for Multiple Myeloma.Frontiers in immunology · 2020Review
- Upregulation of the alternative splicing factor NOVA2 in colorectal cancer vasculature.OncoTargets and therapy · 2018Article
- Anti-cancer Therapies Employing IL-2 Cytokine Tumor Targeting: Contribution of Innate, Adaptive and Immunosuppressive Cells in the Anti-tumor Efficacy.Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo analyze the impact of TNFα or IL2 on human lymphocytes in vitro and the anti-tumor and immune-modifying effects of L19-IL2 and L19-TNFα on subcutaneously growing J558L myeloma in immunocompetent mice.
methodsPBMCs from three healthy volunteers were incubated with IL2, TNFα, or with IL2 plus addition of TNFα (final 20 h). BALB/c J558L mice with subcutaneous tumors were treated with intravenous L19-TNFα plus L19-IL2, or controls. Tumor growth and intra- and peri-tumoral tissues were analyzed for micro-vessel density, necrosis, immune cell composition, and PD1 or PD-L1 expressing cells.
resultsExposure of PBMC in vitro to IL2, TNFα, or to IL2 over 3 and 5 days plus TNFα for the final 20 h resulted in an approximately 50 and 75% reduction of the CD25low effector cell/CD25high Treg cell ratio, respectively, compared to medium control. IL2 or TNFα increased the proportion of CD4- CD25low effector lymphocytes while reducing the proportion of CD4+ CD25low Teff cells. In the J558L myeloma model, tumor eradication was observed in 58, 42, 25, and 0% of mice treated with L19-TNFα plus L19-IL2, L19-TNFα, L19-IL2, and PBS, respectively. L19-TNFα/L19-IL2 combination caused tumor necrosis, capillary density doubling, peri-tumoral T cell and PD1+ T cell reduction (- 50%), and an increase in PD-L1+ myeloma cells.
conclusionIL2, TNFα, or IL2 plus TNFα (final 20 h) increased the proportion of CD4- CD25low effector lymphocytes possibly indicating immune activation. L19-TNFα/L19-IL2 combination therapy eradicated tumors in J558L myeloma BALB/c mice likely via TNFα-induced tumor necrosis and L19-TNFα/L19-IL2-mediated local cellular immune reactions.
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