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

Nat Commun. 2020 Nov 9;11(1):5667. doi: 10.1038/s41467-020-19498-y.

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.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies / administration & dosage*
  • Antibodies / therapeutic use*
  • Cell Line, Tumor
  • Drug Delivery Systems
  • Female
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Immunoconjugates / administration & dosage*
  • Immunoconjugates / therapeutic use*
  • Indoles / administration & dosage
  • Male
  • Middle Aged
  • Non-Randomized Controlled Trials as Topic
  • Panitumumab / administration & dosage
  • Prospective Studies
  • Retrospective Studies

Substances

  • Antibodies
  • Immunoconjugates
  • Indoles
  • Panitumumab

Associated data

  • ClinicalTrials.gov/NCT02415881