Assessing the binding properties of the anti-PD-1 antibody landscape using label-free biosensors

PloS One
Michael E BrownYasmina N Abdiche

Abstract

Here we describe an industry-wide collaboration aimed at assessing the binding properties of a comprehensive panel of monoclonal antibodies (mAbs) against programmed cell death protein 1 (PD-1), an important checkpoint protein in cancer immunotherapy and validated therapeutic target, with well over thirty unique mAbs either in clinical development or market-approved in the United States, the European Union or China. The binding kinetics of the PD-1/mAb interactions were measured by surface plasmon resonance (SPR) using a Carterra LSA instrument and the results were compared to data collected on a Biacore 8K. The effect of chip type on the SPR-derived binding rate constants and affinities were explored and the results compared with solution affinities from Meso Scale Discovery (MSD) and Kinetic Exclusion Assay (KinExA) experiments. When using flat chip types, the LSA and 8K platforms yielded near-identical kinetic rate and affinity constants that matched solution phase values more closely than those produced on 3D-hydrogels. Of the anti-PD-1 mAbs tested, which included a portion of those known to be in clinical development or approved, the affinities spanned from single digit picomolar to nearly 425 nM, challenging the dynamic r...Continue Reading

References

Nov 11, 1999·Journal of Molecular Recognition : JMR·D G Myszka
Apr 23, 2002·Protein Science : a Publication of the Protein Society·Yasmina S N DayDavid G Myszka
Aug 22, 2003·Protein Science : a Publication of the Protein Society·Scott T R WalshAnthony A Kossiakoff
Apr 15, 2004·Analytical Biochemistry·Andrew W DrakeScott L Klakamp
Jul 26, 2005·Biochemical and Biophysical Research Communications·Palaniswami RathanaswamiJohn Babcook
Mar 28, 2006·Analytical Biochemistry·Phinikoula S KatsambaDavid G Myszka
Dec 21, 2010·Analytical Biochemistry·Yasmina N AbdicheArvind Rajpal
Jul 7, 2012·Analytical Biochemistry·Andrew W DrakeScott L Klakamp
Jun 4, 2013·The New England Journal of Medicine·Omid HamidAntoni Ribas
Jan 18, 2017·Proceedings of the National Academy of Sciences of the United States of America·Tushar JainK Dane Wittrup
Feb 7, 2017·Nature Communications·Shuguang TanJinghua Yan
Dec 2, 2017·Nature Reviews. Drug Discovery·Paul J Carter, Greg A Lazar
Jan 31, 2018·Nature Reviews. Immunology·Laura M Walker, Dennis R Burton
Jul 6, 2018·Frontiers in Oncology·Frank Stenner, Christoph Renner
Dec 6, 2018·MAbs·Hélène Kaplon, Janice M Reichert
Mar 29, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hyun Tae LeeYong-Seok Heo
May 28, 2019·The Journal of Experimental Medicine·Craig FenwickGiuseppe Pantaleo
Aug 29, 2019·Scientific Reports·Aravindhan GanesanKhaled Barakat

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Methods Mentioned

BETA
surface plasmon resonance
chip
chips
biosensor
FACS
Kinetic
affinity

Software Mentioned

KinExA Pro
Carterra Kinetic tool
Biacore 8K Evaluation
Prism
KinExA

Related Concepts

Related Feeds

Cancer Vaccines

Cancer vaccines are vaccines that either treat existing cancer or prevent development of a cancer.