ArticleThe Journal of clinical investigation2000
Melanoma immunotherapy by targeted IL-2 depends on CD4(+) T-cell help mediated by CD40/CD40L interaction.
Article in The Journal of clinical investigation, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 41 citations in OpenAlex.
- Immune-mediated Engagement of T Regulatory Cells with Tumor Cells Results in Trogocytosis and Tumor Cell Killing.bioRxiv : the preprint server for biology · 2025Article
- ROR2-specific CAR T cells are effective against hematologic and solid tumors and well tolerated in mice.Cell reports. Medicine · 2025Article
- GD2-targeting therapy: a comparative analysis of approaches and promising directions.Frontiers in immunology · 2024Review
- Utilizing Immunocytokines for Cancer Therapy.Antibodies (Basel, Switzerland) · 2021Review
- Anti-GD2 mAbs and next-generation mAb-based agents for cancer therapy.Immunotherapy · 2016Review
- Immunocytokines and bispecific antibodies: two complementary strategies for the selective activation of immune cells at the tumor site.Immunological reviews · 2016Review
- Tailoring the Treatment of Melanoma: Implications for Personalized Medicine.The Yale journal of biology and medicine · 2015Review
- Systemically transplanted human gingiva-derived mesenchymal stem cells contributing to bone tissue regeneration.International journal of clinical and experimental pathology · 2014Article
- Agonistic anti-CD40 promotes early development and increases the incidence of severe thyroid epithelial cell hyperplasia (TEC H/P) in CD4-/- mice.Immunity, inflammation and disease · 2013Article
- Advances in lupus stemming from the parent-into-F1 model.Trends in immunology · 2010Review
- IL-4 suppresses very late antigen-4 expression which is required for therapeutic Th1 T-cell trafficking into tumors.Journal of immunotherapy (Hagerstown, Md. : 1997) · 2009Article
- CTL-promoting effects of CD40 stimulation outweigh B cell-stimulatory effects resulting in B cell elimination and disease improvement in a murine model of lupus.Journal of immunology (Baltimore, Md. : 1950) · 2008Article
- Therapeutic efficacy of tumor-targeted IL2 in LTalpha(-/-) mice depends on conditioned T cells.Cancer immunology, immunotherapy : CII · 2006Article
- Rescue of CD8 T cell-mediated antimicrobial immunity with a nonspecific inflammatory stimulus.The Journal of clinical investigation · 2002Article
- Expression of a "self-"antigen by human tumor cells enhances tumor antigen-specific CD4(+) T-cell function.Cancer research · 2002Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The induction of tumor-protective immunity against malignancies remains a major challenge in cancer immunotherapy. A novel, humanized anti-ganglioside-GD(2)-IL-2 immunocytokine (hu14.18-IL-2) induced CD8(+) T cells to eradicate established pulmonary metastases of B78-D14 murine melanoma, in a process that required help by CD4(+) T cells and was mediated by the CD40/CD40 ligand (CD40L) interaction. The anti-tumor effect was diminished in mice deficient in CD4(+) T-cells. Three lines of evidence show that CD4(+) T-cell help was mediated by CD40/CD40L interaction but not by endogenous IL-2 production. First, the hu14.18-IL-2-induced anti-tumor response is partially abrogated in C57BL/6J CD40L knockout (KO) mice in contrast to C57BL/6J IL-2 KO animals, in which the immunocytokine was completely effective. Second, partial abrogation of the anti-tumor effect is induced with anti-CD40L antibodies to the same extent as with CD4(+) T-cell depletion. Third, a complete anti-tumor response induced by hu14.18-IL-2 can be reconstituted in C57BL/6J CD40L KO mice by simultaneous stimulation with an anti-CD40 mAb. These results suggest that help provided by CD4(+) T cells via CD40/CD40L interactions in our tumor model is crucial for effective immunotherapy with an IL-2 immunocytokine.
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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.