ArticleOncoimmunology2016
Successful engineering of a highly potent single-chain variable-fragment (scFv) bispecific antibody to target disialoganglioside (GD2) positive tumors.
Article in Oncoimmunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 39 citations in OpenAlex.
- Bispecific antibodies and CAR T cells targeting a TP53 mutation-associated neoantigen show discordant affinity requirements.The Journal of clinical investigation · 2026Article
- Beyond the chimeric antigen receptor T cells and bispecific antibody duopoly: ex vivo armed T cells for solid tumors.Frontiers in immunology · 2026Review
- BAFF-based trifunctional T-cell engagers trigger robust tumor immunity against B-cell malignancies.Protein & cell · 2025Article
- Dual targeting of tumoral cells and immune microenvironment by blocking the IL-33/IL1RL1 pathway.Nature communications · 2025Article
- Biology of GD2 ganglioside: implications for cancer immunotherapy.Frontiers in pharmacology · 2023Review
- Smaller size packs a stronger punch - Recent advances in small antibody fragments targeting tumour-associated carbohydrate antigens.Theranostics · 2023Review
- Bispecific antibodies for the treatment of neuroblastoma.Pharmacology & therapeutics · 2022Review
- Review
- Novel potent anti-STEAP1 bispecific antibody to redirect T cells for cancer immunotherapy.Journal for immunotherapy of cancer · 2021Article
- GD2-directed bispecific trifunctional antibody outperforms dinutuximab beta in a murine model for aggressive metastasized neuroblastoma.Journal for immunotherapy of cancer · 2021Article
- The Role of Sphingolipids in Cancer Immunotherapy.International journal of molecular sciences · 2021Review
- Tumor-Associated Glycans as Targets for Immunotherapy: The Wistar Institute Experience/Legacy.Monoclonal antibodies in immunodiagnosis and immunotherapy · 2021Review
- Targeting a neoantigen derived from a commonScience (New York, N.Y.) · 2021Article
- A Self-Assembling and Disassembling (SADA) Bispecific Antibody (BsAb) Platform for Curative Two-step Pretargeted Radioimmunotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Integrin-directed antibody-based immunotherapy: focus on VLA-4.Immunotherapy advances · 2021Review
- Overcoming leukemia heterogeneity by combining T cell engaging bispecific antibodies.Journal for immunotherapy of cancer · 2020Article
- Epithelial Ovarian Cancer and the Immune System: Biology, Interactions, Challenges and Potential Advances for Immunotherapy.Journal of clinical medicine · 2020Review
- Designing a new bispecific tandem single-chain variable fragment antibody against tumor necrosis factor-α and interleukin-23 using in silico studies for the treatment of rheumatoid arthritis.Journal of molecular modeling · 2020Article
- Targets and Antibody Formats for Immunotherapy of Neuroblastoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020Review
- Interdomain spacing and spatial configuration drive the potency of IgG-[L]-scFv T cell bispecific antibodies.Science translational medicine · 2020Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Engineering potent bispecific antibodies from single-chain variable fragments (scFv) remains difficult due to the inherent instability and insufficient binding of scFv's compared to their parental immunoglobulin format. Previously, we described a scFv-based bispecific antibody (scBA) against disialoganglioside (GD2) based on the anti-GD2 murine 5F11-scFv and the anti-CD3 huOKT3-scFv (5F11-scBA). In this study, we substituted the 5F11-scFv with the higher affinity (13-fold) hu3F8-scFv to form hu3F8-scBA. With this modification, hu3F8-scBA redirected T cells to kill GD2(+) cancer cell lines with up to 5,000-fold higher potency (femtomolar EC50) compared with 5F11-scBA (picomolar EC50) in cytotoxicity assays, even against target cells with low GD2 densities. Furthermore, hu3F8-scBA induced stronger T-cell activation than 5F11-scBA, as measured by Ca(2+) flux and cytokine release. Additionally, in vivo, hu3F8-scBA suppressed tumor growth and prolonged mice survival much more effectively than 5F11-scBA, in both neuroblastoma and melanoma xenograft models. We conclude that the functional properties of scBA's can be increased substantially by relatively modest increases in antigen affinity.
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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.