The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
A Potent Anti-CD70 Antibody–Drug Conjugate Combining a Dimeric Pyrrolobenzodiazepine Drug with Site-Specific Conjugation Technology
Abstract
A highly cytotoxic DNA cross-linking pyrrolobenzodiazepine (PBD) dimer with a valine-alanine dipeptide linker was conjugated to the anti-CD70 h1F6 mAb either through endogenous interchain cysteines or, site-specifically, through engineered cysteines at position 239 of the heavy chains. The h1F6239C-PBD conjugation strategy proved to be superior to interchain cysteine conjugation, affording an antibody-drug conjugate (ADC) with high uniformity in drug-loading and low levels of aggregation. In vitro cytotoxicity experiments demonstrated that the h1F6239C-PBD was potent and immunologically specific on CD70-positive renal cell carcinoma (RCC) and non-Hodgkin lymphoma (NHL) cell lines. The conjugate was resistant to drug loss in plasma and in circulation, and had a pharmacokinetic profile closely matching that of the parental h1F6239C antibody capped with N-ethylmaleimide (NEM). Evaluation in CD70-positive RCC and NHL mouse xenograft models showed pronounced antitumor activities at single or weekly doses as low as 0.1 mg/kg of ADC. The ADC was tolerated at 2.5 mg/kg. These results demonstrate that PBDs can be effectively used for antibody-targeted therapy.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Walsh, N., Larkin, A., Kennedy, S., Connolly, L., Ballot, J., Ooi, W., Gullo, G., Crown, J., Clynes, M., & O'Driscoll, L. (2009) · BMC Urology · doi:10.1186/1471-2490-9-6 · Cited by 88
Cited by
Strategies and challenges for the next generation of antibody–drug conjugates
Beck, A., Goetsch, L., Dumontet, C., & Corvaïa, N. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.268 · Cited by 2,271
Antibody–Drug Conjugates: An Emerging Concept in Cancer Therapy
Chari, R. V. J., Miller, M. L., & Widdison, W. C. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201307628 · Cited by 930
Agarwal, P., & Bertozzi, C. R. (2015) · Bioconjugate Chemistry · doi:10.1021/bc5004982 · Cited by 605
Lyon, R. P., Bovee, T. D., Doronina, S. O., Burke, P. J., Hunter, J. H., Neff-LaFord, H. D., Jonas, M., Anderson, M. E., Setter, J. R., & Senter, P. D. (2015) · Nature Biotechnology · doi:10.1038/nbt.3212 · Cited by 557
Self-citationLyon, R. P., Setter, J. R., Bovee, T. D., Doronina, S. O., Hunter, J. H., Anderson, M. E., Balasubramanian, C. L., Duniho, S. M., Leiske, C. I., Li, F., et al. (2014) · Nature Biotechnology · doi:10.1038/nbt.2968 · Cited by 461
Self-citation
Metadata
- Authors
- Jeffrey, S. C., Burke, P. J., Lyon, R. P., Meyer, D. W., Sussman, D., Anderson, M., Hunter, J. H., Leiske, C. I., Miyamoto, J. B., Nicholas, N. D., Okeley, N. M., Sanderson, R. J., Stone, I. J., Zeng, W., Gregson, S. J., Masterson, L., Tiberghien, A. C., Howard, P. W., Thurston, D. E., Law, C.-L., & Senter, P. D.
- Venue
- Bioconjugate Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2013-06-28
- Volume
- 24
- Issue
- 7
- Pages
- 1256-1263
- ISSN
- 1043-1802 (ISSN-L)
- 1520-4812
- OpenAlex
- W2052768531
- Cited by
- 245
- References
- 1
- FWCI
- 12.35
- Type
- journal article
- Language
- en
- Open access
- closed
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
