Jump to main content
Jump to site search


Leucine-rich alpha-2-glycoprotein 1 (LRG1) as a novel ADC target

Author affiliations

Abstract

Leucine-rich alpha-2-glycoprotein 1 (LRG1) is present abundantly in the microenvironment of many tumours where it contributes to vascular dysfunction, which impedes the delivery of therapeutics. In this work we demonstrate that LRG1 is predominantly a non-internalising protein. We report the development of a novel antibody–drug conjugate (ADC) comprising the anti-LRG1 hinge-stabilised IgG4 monoclonal antibody Magacizumab coupled to the anti-mitotic payload monomethyl auristatin E (MMAE) via a cleavable dipeptide linker using the site-selective disulfide rebridging dibromopyridazinedione (diBrPD) scaffold. It is demonstrated that this ADC retains binding post-modification, is stable in serum and effective in in vitro cell studies. We show that the extracellular LRG1-targeting ADC provides an increase in survival in vivo when compared against antibody alone and similar anti-tumour activity when compared against standard chemotherapy, but without undesired side-effects. LRG1 targeting through this ADC presents a novel and effective proof-of-concept en route to improving the efficacy of cancer therapeutics.

Graphical abstract: Leucine-rich alpha-2-glycoprotein 1 (LRG1) as a novel ADC target

Back to tab navigation

Supplementary files

Article information


Submitted
06 May 2021
Accepted
27 May 2021
First published
31 May 2021

This article is Open Access

RSC Chem. Biol., 2021, Advance Article
Article type
Communication

Leucine-rich alpha-2-glycoprotein 1 (LRG1) as a novel ADC target

F. Javaid, C. Pilotti, C. Camilli, D. Kallenberg, C. Bahou, J. Blackburn, J. R. Baker, J. Greenwood, S. E. Moss and V. Chudasama, RSC Chem. Biol., 2021, Advance Article , DOI: 10.1039/D1CB00104C

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material.

Reproduced material should be attributed as follows:

  • For reproduction of material from NJC:
    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
  • For reproduction of material from PCCP:
    [Original citation] - Published by the PCCP Owner Societies.
  • For reproduction of material from PPS:
    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
  • For reproduction of material from all other RSC journals:
    [Original citation] - Published by The Royal Society of Chemistry.

Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.


Social activity

Search articles by author

Spotlight

Advertisements