ArticlemAbs
Sortase-catalyzed in vitro functionalization of a HER2-specific recombinant Fab for tumor targeting of the plant cytotoxin gelonin.
Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 55 citations in OpenAlex.
- Review
- Recombinant immunotoxins development for HER2-based targeted cancer therapies.Cancer cell international · 2021Review
- Chemically Crosslinked Bispecific Antibodies for Cancer Therapy: Breaking from the Structural Restrictions of the Genetic Fusion Approach.International journal of molecular sciences · 2020Article
- CAR, a Homing Peptide, Prolongs Pulmonary Preferential Vasodilation by Increasing Pulmonary Retention and Reducing Systemic Absorption of Liposomal Fasudil.Molecular pharmaceutics · 2019Article
- A Sortase A Programmable Phage Display Format for Improved Panning of Fab Antibody Libraries.Journal of molecular biology · 2018Article
- Enzyme-Based Labeling Strategies for Antibody-Drug Conjugates and Antibody Mimetics.Antibodies (Basel, Switzerland) · 2018Review
- The activity of myeloid cell-specific VHH immunotoxins is target-, epitope-, subset- and organ dependent.Scientific reports · 2017Article
- A Versatile Chemo-Enzymatic Conjugation Approach Yields Homogeneous and Highly Potent Antibody-Drug Conjugates.International journal of molecular sciences · 2017Article
- Proximity-Based Sortase-Mediated Ligation.Angewandte Chemie (International ed. in English) · 2017Article
- Affinity Maturation of a Cyclic Peptide Handle for Therapeutic Antibodies Using Deep Mutational Scanning.The Journal of biological chemistry · 2017Article
- Spontaneous Isopeptide Bond Formation as a Powerful Tool for Engineering Site-Specific Antibody-Drug Conjugates.Scientific reports · 2016Article
- Hapten-directed spontaneous disulfide shuffling: a universal technology for site-directed covalent coupling of payloads to antibodies.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Article
- Antibody drug conjugates: design and selection of linker, payload and conjugation chemistry.The AAPS journal · 2015Review
- Sortase Enzyme-Mediated Generation of Site-Specifically Conjugated Antibody Drug Conjugates with High In Vitro and In Vivo Potency.PloS one · 2015Article
- Bifunctional fused polypeptide inhibits the growth and metastasis of breast cancer.Drug design, development and therapy · 2015Article
- Peptide-coated liposomal fasudil enhances site specific vasodilation in pulmonary arterial hypertension.Molecular pharmaceutics · 2014Article
- Bispecific antibody generated with sortase and click chemistry has broad antiinfluenza virus activity.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- PAS-cal: a generic recombinant peptide calibration standard for mass spectrometry.Journal of the American Society for Mass Spectrometry · 2014Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We report on the preparation of a new type of immunotoxin via in vitro ligation of the αHer2 antigen binding fragment (Fab) of the clinically-validated antibody trastuzumab to the plant toxin gelonin, employing catalysis by the bacterial enzyme sortase A (SrtA). The αHer2 Fab was fused with the extended SrtA recognition motif LPET↓GLEH 6 at the C-terminus of its heavy chain, thereby preventing interference with antigen binding, while the toxin was equipped with a Gly 2 sequence at its N-terminus, distant to the catalytically active site in the C-terminal region. Site-specific in vitro transpeptidation led to a novel antibody-toxin conjugate wherein gelonin had effectively replaced the Fc region of a conventional (monomerized) immunoglobulin. After optimization of reaction conditions and incubation time, the resulting Fab-Gelonin ligation product was purified to homogeneity in a two-step procedure by means of Strep-Tactin affinity chromatography--utilizing the Strep-tag II appended to gelonin--and size exclusion chromatography. Binding activity of the immunotoxin for the Her2 ectodomain was indistinguishable from the unligated Fab as measured by real-time surface plasmon resonance spectroscopy. Specific cytotoxic potency of Fab-Gelonin was demonstrated against two Her2-positive cell lines, resulting in EC 50 values of ~1 nM or lower, indicating a 1000-fold enhanced cell-killing activity compared with gelonin itself. Thus, our strategy provides a convenient route to the modular construction of functional immunotoxins from Fabs of established tumor-specific antibodies with gelonin or related proteotoxins, also avoiding the elevated biosafety levels that would be mandatory for the direct biotechnological preparation of corresponding fusion proteins.
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.