ArticleMolecular cancer therapeutics2023
Payload-Binding Fab Fragments Increase the Therapeutic Index of MMAE Antibody-Drug Conjugates.
Article in Molecular cancer therapeutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Efficacy and safety of antibody-drug conjugate based therapy in locally advanced or metastatic urothelial carcinoma: a systematic review and network meta-analysis of emerging clinical evidence.Frontiers in immunology · 2026Pooled it
- Antibody-Drug Conjugates and Peptide-Drug Conjugates: Current Understandings and Future Perspectives.MedComm · 2026Review
- Multimerization and Conjugation to Antiviral and Cytotoxic Payloads Enhance the Activity of Virus-Neutralizing Nanobodies In Vitro.ACS omega · 2026Article
- Antibody-drug conjugates in breast cancer: from mechanism to revolutionizing clinical practice.Molecular cancer · 2026Review
- Precision theranostics in oncology: integrating antibody-drug conjugates, radioimmunotherapy, and immuno‑PET for adaptive cancer care.Discover oncology · 2026Review
- Focusing on toxicity management: Challenges and strategies for HER2-targeted antibody-drug conjugates in breast cancer.Breast (Edinburgh, Scotland) · 2026Review
- Bench-to-Bedside Perspectives on Ocular Toxicity of Antibody-Drug Conjugates: Toxicology, Clinical Management and Molecule Optimization.Pharmaceutical research · 2026Review
- Antibody-drug conjugates for primary brain tumors.Frontiers in oncology · 2026Review
- Unveiling the molecular and immunological drivers of antibody-drug conjugates in cancer treatment.Nature reviews. Cancer · 2025Review
- Assessment of ADC Higher Order Structure Through 2D NMR Analysis.Molecules (Basel, Switzerland) · 2025Article
- A dual-targeting peptide-drug conjugate based on CXCR4 and FOLR1 inhibits triple-negative breast cancer.Acta pharmaceutica Sinica. B · 2025Article
- Antibody-Drug Conjugates in Breast Cancer: Navigating Innovations, Overcoming Resistance, and Shaping Future Therapies.Biomedicines · 2025Review
- Camptothein-Based Anti-Cancer Therapies and Strategies to Improve Their Therapeutic Index.Cancers · 2025Review
- Opportunities and Challenges in Antibody-Drug Conjugates for Cancer Therapy: A New Era for Cancer Treatment.Cancers · 2025Review
- Antibody-drug conjugate: a newly developed biological missile for tumor treatment.Frontiers in oncology · 2025Review
- Efficacy and safety of antibody-drug conjugates in the treatment of advanced urological cancers: a systematic review and a meta-analysis.Frontiers in pharmacology · 2025Review
- A case of karyomegalic interstitial nephritis without FAN1 mutations in the setting of brentuximab, ifosfamide, and carboplatin exposure.BMC nephrology · 2024Article
- Aligning fermentation conditions with non-canonical amino acid addition strategy is essential for Nε-((2-azidoethoxy)carbonyl)-L-lysine uptake and incorporation into the target protein.Scientific reports · 2024Article
- Novel Anti-Trop2 Nanobodies Disrupt Receptor Dimerization and Inhibit Tumor Cell Growth.Pharmaceutics · 2024Article
- Antibody-drug conjugates in solid tumors; new strategy for cancer therapy.Japanese journal of clinical oncology · 2024Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Monomethyl auristatin E (MMAE) is a potent tubulin inhibitor that is used as the payload for four FDA-approved antibody-drug conjugates (ADC). Deconjugated MMAE readily diffuses into untargeted cells, resulting in off-target toxicity. Here, we report the development and evaluation of a humanized Fab fragment (ABC3315) that enhances the therapeutic selectivity of MMAE ADCs. ABC3315 increased the IC50 of MMAE against human cancer cell lines by > 500-fold with no impact on the cytotoxicity of MMAE ADCs, including polatuzumab vedotin (PV) and trastuzumab-vc-MMAE (TvcMMAE). Coadministration of ABC3315 did not reduce the efficacy of PV or TvcMMAE in xenograft tumor models. Coadministration of ABC3315 with 80 mg/kg TvcMMAE significantly (P < 0.0001) increased the cumulative amount of MMAE that was excreted in urine 0 to 4 days after administration from 789.4±19.0 nanograms (TvcMMAE alone) to 2625±206.8 nanograms (for mice receiving TvcMMAE with coadministration of ABC3315). Mice receiving 80 mg/kg TvcMMAE and PBS exhibited a significant drop in white blood cell counts (P = 0.025) and red blood cell counts (P = 0.0083) in comparison with control mice. No significant differences, relative to control mice, were found for white blood cell counts (P = 0.15) or for red blood cell counts (P = 0.23) for mice treated with 80 mg/kg TvcMMAE and ABC3315. Coadministration of ABC3315 with 120 mg/kg PV significantly (P = 0.045) decreased the percentage body weight loss at nadir for treated mice from 11.9%±7.0% to 4.1%±2.1%. Our results demonstrate that ABC3315, an anti-MMAE Fab fragment, decreases off-target toxicity while not decreasing antitumor efficacy, increasing the therapeutic window of MMAE ADCs.
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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.