ArticleJournal for immunotherapy of cancer2020
First in human dose calculation of a single-chain bispecific antibody targeting glioma using the MABEL approach.
Article in Journal for immunotherapy of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Checkpoint inhibitor immunotherapy for glioblastoma: current progress, challenges and future outlook.Expert review of clinical pharmacology · 2020Pooled it
- MAGE-A4/MAGE-A8-targeted TCR-based bispecific T cell engager in recurrent and/or refractory solid tumors: a phase 1 trial.Nature medicine · 2026Article
- Application of new approach methodologies for nonclinical safety assessment of drug candidates.Nature reviews. Drug discovery · 2025Review
- IL-7-mediated expansion of autologous lymphocytes increases CD8bioRxiv : the preprint server for biology · 2025Article
- Towards in vitro models for reducing or replacing the use of animals in drug testing.Nature biomedical engineering · 2024Article
- A novel T cell-redirecting anti-GPRC5D × CD3 bispecific antibody with potent antitumor activity in multiple myeloma preclinical models.Scientific reports · 2024Article
- Development of bispecific T cell engagers: harnessing quantitative systems pharmacology.Trends in pharmacological sciences · 2023Review
- Bispecific T-Cell Engagers and Chimeric Antigen Receptor T-Cell Therapies in Glioblastoma: An Update.Current oncology (Toronto, Ont.) · 2023Review
- Bispecific antibody targeting TGF-β and PD-L1 for synergistic cancer immunotherapy.Frontiers in immunology · 2023Review
- Determination of starting dose of the T cell-redirecting bispecific antibody ERY974 targeting glypican-3 in first-in-human clinical trial.Scientific reports · 2022Article
- The inhibitory effect of human umbilical cord mesenchymal stem cells expressing anti-HAAH scFv-sTRAIL fusion protein on glioma.Frontiers in bioengineering and biotechnology · 2022Article
- For whom the T cells troll? Bispecific T-cell engagers in glioblastoma.Journal for immunotherapy of cancer · 2021Review
- Fc-comprising scDb-based trivalent, bispecific T-cell engagers for selective killing of HER3-expressing cancer cells independent of cytokine release.Journal for immunotherapy of cancer · 2021Article
- Bispecific Immunomodulatory Antibodies for Cancer Immunotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Review
- A Rational Designed Novel Bispecific Antibody for the Treatment of GBM.Biomedicines · 2021Article
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- Modeling Pharmacokinetics and Pharmacodynamics of Therapeutic Antibodies: Progress, Challenges, and Future Directions.Pharmaceutics · 2021Review
- Monoclonal Antibodies as Neurological Therapeutics.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Malignant Tumor Purity Reveals the Driven and Prognostic Role ofFrontiers in oncology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundFirst-in-human (FIH) clinical trials require careful selection of a safe yet biologically relevant starting dose. Typically, such starting doses are selected based on toxicity studies in a pharmacologically relevant animal model. However, with the advent of target-specific and highly active immunotherapeutics, both the Food and Drug Administration and the European Medicines Agency have provided guidance that recommend determining a safe starting dose based on a minimum anticipated biological effect level (MABEL) approach.
methodsWe recently developed a T cell activating bispecific antibody that effectively treats orthotopic patient-derived malignant glioma and syngeneic glioblastoma in mice (hEGFRvIII:CD3 bi-scFv). hEGFRvIII:CD3 bi-scFv is comprized of two single chain antibody fragments (bi-scFvs) that bind mutant epidermal growth factor receptor variant III (EGFRvIII), a mutation frequently seen in malignant glioma, and human CD3ε on T cells, respectively. In order to establish a FIH dose, we used a MABEL approach to select a safe starting dose for hEGFRvIII:CD3 bi-scFv, based on a combination of in vitro data, in vivo animal studies, and theoretical human receptor occupancy modeling.
resultsUsing the most conservative approach to the MABEL assessment, a dose of 57.4 ng hEGFRvIII:CD3 bi-scFv/kg body weight was selected as a safe starting dose for a FIH clinical study.
conclusionsThe comparison of our MABEL-based starting dose to our in vivo efficacious dose and the theoretical human receptor occupancy strongly supports that our human starting dose of 57.4 ng hEGFRvIII:CD3 bi-scFv/patient kg will be safe.
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