ArticleOncoimmunology
Advancing targeted co-stimulation with antibody-fusion proteins by introducing TNF superfamily members in a single-chain format.
Article in Oncoimmunology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Generation and characterization of OX40-ligand fusion protein that agonizes OX40 on T-Lymphocytes.Frontiers in immunology · 2024Article
- Article
- Development of an antibody-ligand fusion protein scFvCD16AMicrobial cell factories · 2023Article
- Design and selection of anti-PD-L1 single-domain antibody and tumor necrosis factor superfamily ligands for an optimal vectorization in an oncolytic virus.Frontiers in bioengineering and biotechnology · 2023Article
- Targeting Co-Stimulatory Receptors of the TNF Superfamily for Cancer Immunotherapy.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- Fc-based Duokines: dual-acting costimulatory molecules comprising TNFSF ligands in the single-chain format fused to a heterodimerizing Fc (scDk-Fc).Oncoimmunology · 2022Article
- A scDb-based trivalent bispecific antibody for T-cell-mediated killing of HER3-expressing cancer cells.Scientific reports · 2021Article
- Co-Stimulatory Bispecific Antibodies Induce Enhanced T Cell Activation and Tumor Cell Killing in Breast Cancer Models.Frontiers in immunology · 2021Article
- Engineering of a trispecific tumor-targeted immunotherapy incorporating 4-1BB co-stimulation and PD-L1 blockade.Oncoimmunology · 2021Article
- Pharmacokinetic Engineering of OX40-Blocking Anticalin Proteins Using Monomeric Plasma Half-Life Extension Domains.Frontiers in pharmacology · 2021Article
- Evaluation of switch-mediated costimulation in trans on universal CAR-T cells (UniCAR) targeting CD123-positive AML.Oncoimmunology · 2021Article
- An engineered 4-1BBL fusion protein with "activity on demand".Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Influence of antigen density and immunosuppressive factors on tumor-targeted costimulation with antibody-fusion proteins and bispecific antibody-mediated T cell response.Cancer immunology, immunotherapy : CII · 2020Article
- A universal reporter cell line for bioactivity evaluation of engineered cytokine products.Scientific reports · 2020Article
- Antibody-cytokine fusion proteins: A novel class of biopharmaceuticals for the therapy of cancer and of chronic inflammation.New biotechnology · 2019Review
- Tumor-targeted 4-1BB agonists for combination with T cell bispecific antibodies as off-the-shelf therapy.Science translational medicine · 2019Article
- Carcinoembryonic Antigen (CEA)-Specific 4-1BB-Costimulation Induced by CEA-Targeted 4-1BB-Agonistic Trimerbodies.Frontiers in immunology · 2019Article
- A tumor-targeted trimeric 4-1BB-agonistic antibody induces potent anti-tumor immunity without systemic toxicity.Nature communications · 2018Article
- Potentiation of PD-L1 blockade with a potency-matched dual cytokine-antibody fusion protein leads to cancer eradication in BALB/c-derived tumors but not in other mouse strains.Cancer immunology, immunotherapy : CII · 2018Article
- A novel dual-cytokine-antibody fusion protein for the treatment of CD38-positive malignancies.Protein engineering, design & selection : PEDS · 2018Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Co-stimulation via receptors of the tumor necrosis factor superfamily (TNFSF) emerges as promising strategy to support antitumor immune responses. Targeted strategies with antibody-fusion proteins composed of a tumor-directed antibody part and the extracellular domain of a co-stimulatory ligand of the TNFSF constitute an attractive option to focus the co-stimulatory activity to the tumor site. Since TNFSF members intrinsically form functional units of non-covalently linked homotrimers, the protein engineering of suitable antibody-fusion proteins is challenging. Aiming for molecules of simple and stable configuration, we used TNFSF ligands in a single-chain format (scTNFSF), i.e., three units of the ectodomain connected by polypeptide linkers, folding into an intramolecular trimer. By fusing tumor-directed scFv antibody fragments directed against EpCAM or FAP to co-stimulatory scTNFSF molecules (sc4-1BBL, scOX40L, scGITRL or scLIGHT), a set of monomeric scFv-scTNFSF fusion proteins was generated. In comparison to the scFv-TNFSF format, defined by intermolecular homotrimerization via the TNFSF part, scFv-scTNFSF showed equal or enhanced co-stimulatory activity despite reduced avidity in antibody binding. In addition, enhanced serum stability and improved bioavailability in mice were observed. We show that the scFv-scTNFSF format can be applied to various members of the TNFSF, presenting targeting-dependent co-stimulatory activity. Hence, this format exhibits favorable properties that make it a promising choice for further therapeutic fusion protein development.
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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.