Co-administered antibody improves penetration of antibody–dye conjugate into human cancers with implications for antibody–drug conjugates

Guolan Lu, Naoki Nishio, Nynke S. Berg, Brock A. Martin, Shayan Fakurnejad, Stan Keulen, Alexander D. Colevas, Greg M. Thurber and Eben L. Rosenthal ()
Additional contact information
Guolan Lu: Stanford University School of Medicine
Naoki Nishio: Stanford University School of Medicine
Nynke S. Berg: Stanford University School of Medicine
Brock A. Martin: Stanford University School of Medicine
Shayan Fakurnejad: Stanford University School of Medicine
Stan Keulen: Stanford University School of Medicine
Alexander D. Colevas: Stanford University School of Medicine
Greg M. Thurber: University of Michigan
Eben L. Rosenthal: Stanford University School of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: Abstract Poor tissue penetration remains a major challenge for antibody-based therapeutics of solid tumors, but proper dosing can improve the tissue penetration and thus therapeutic efficacy of these biologics. Due to dose-limiting toxicity of the small molecule payload, antibody-drug conjugates (ADCs) are administered at a much lower dose than their parent antibodies, which further reduces tissue penetration. We conducted an early-phase clinical trial (NCT02415881) and previously reported the safety of an antibody-dye conjugate (panitumumab-IRDye800CW) as primary outcome. Here, we report a retrospective exploratory analysis of the trial to evaluate whether co-administration of an unconjugated antibody could improve the intratumoral distribution of the antibody-dye conjugate in patients. By measuring the multiscale distribution of the antibody-dye conjugate, this study demonstrates improved microscopic antibody distribution without increasing uptake (toxicity) in healthy tissue when co-administered with the parent antibody, supporting further clinical investigation of the co-administration dosing strategy to improve the tumor penetration of ADCs.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-19498-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19498-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-19498-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().