ArticleCancer immunology, immunotherapy : CII2011
Ab-IL2 fusion proteins mediate NK cell immune synapse formation by polarizing CD25 to the target cell-effector cell interface.
Article in Cancer immunology, immunotherapy : CII, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 38 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
- A novel nanobody-based immunocytokine of a mutant interleukin-2 as a potential cancer therapeutic.AMB Express · 2024Article
- Targeted Cytokine Delivery for Cancer Treatment: Engineering and Biological Effects.Pharmaceutics · 2023Review
- Potent immunomodulatory and antitumor effect of anti-CD20-IL2no-alpha tri-functional immunocytokine for cancer therapy.Frontiers in immunology · 2022Article
- Utilizing Immunocytokines for Cancer Therapy.Antibodies (Basel, Switzerland) · 2021Review
- MUC16 suppresses human and murine innate immune responses.Gynecologic oncology · 2019Article
- Enhanced Therapeutic Activity of Non-Internalizing Small-Molecule-Drug Conjugates Targeting Carbonic Anhydrase IX in Combination with Targeted Interleukin-2.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Addressing the Immunogenicity of the Cargo and of the Targeting Antibodies with a Focus on Demmunized Bacterial Toxins and on Antibody-Targeted Human Effector Proteins.Biomedicines · 2017Review
- Is immunity in cancer the key to improving clinical outcome?: Report on the International Symposium on Immunotherapy, The Royal Society, London, UK, 12-13 May 2017.Therapeutic advances in vaccines · 2017Article
- Delivering safer immunotherapies for cancer.Advanced drug delivery reviews · 2017Review
- Interleukin-2: Old and New Approaches to Enhance Immune-Therapeutic Efficacy.Advances in experimental medicine and biology · 2017Review
- In Situ Tumor Vaccination by Combining Local Radiation and Tumor-Specific Antibody or Immunocytokine Treatments.Cancer research · 2016Article
- Immunocytokines for cancer treatment: past, present and future.Current opinion in immunology · 2016Review
- Production of an active anti-CD20-hIL-2 immunocytokine in Nicotiana benthamiana.Plant biotechnology journal · 2016Article
- Enhancing Cancer Immunotherapy Via Activation of Innate Immunity.Seminars in oncology · 2015Review
- NK cell-based immunotherapies in Pediatric Oncology.Journal of pediatric hematology/oncology · 2015Review
- NK Cell-Mediated Antibody-Dependent Cellular Cytotoxicity in Cancer Immunotherapy.Frontiers in immunology · 2015Review
- Challenges and developing solutions for increasing the benefits of IL-2 treatment in tumor therapy.Expert review of clinical immunology · 2014Review
- Differential expression of proteins in naïve and IL-2 stimulated primary human NK cells identified by global proteomic analysis.Journal of proteomics · 2013Article
- Immunocytokines: a review of molecules in clinical development for cancer therapy.Clinical pharmacology : advances and applications · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
The huKS-IL2 immunocytokine (IC) consists of IL2 fused to a mAb against EpCAM, while the hu14.18-IL2 IC recognizes the GD2 disialoganglioside. They are under evaluation for treatment of EpCAM(+) (ovarian) and GD2(+) (neuroblastoma and melanoma) malignancies because of their proven ability to enhance tumor cell killing by antibody-dependent cell-mediated cytotoxicity (ADCC) and by antitumor cytotoxic T cells. Here, we demonstrate that huKS-IL2 and hu14.18-IL2 bind to tumor cells via their antibody components and increase adhesion and activating immune synapse (AIS) formation with NK cells by engaging the immune cells' IL-2 receptors (IL2R). The NK leukemia cell line, NKL (which expresses high affinity IL2Rs), shows fivefold increase in binding to tumor targets when treated with IC compared to matching controls. This increase in binding is effectively inhibited by blocking antibodies against CD25, the α-chain of the IL2R. NK cells isolated from the peritoneal environment of ovarian cancer patients, known to be impaired in mediating ADCC, bind to huKS-IL2 via CD25. The increased binding between tumor and effector cells via ICs is due to the formation of AIS that are characterized by the simultaneous polarization of LFA-1, CD2 and F-actin at the cellular interface. AIS formation of peritoneal NK and NKL cells is inhibited by anti-CD25 blocking antibody and is 50-200% higher with IC versus the parent antibody. These findings demonstrate that the IL-2 component of the IC allows IL2Rs to function not only as receptors for this cytokine but also as facilitators of peritoneal NK cell binding to IC-coated tumor cells.
Indexed as
Identifiers
What OpenQuestion holds
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.