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Serum albumin: a pharmacokinetic marker for optimizing treatment outcome of immune checkpoint blockade

As we look forward to the bright future of immune checkpoint blockade (ICB) therapy, there is still lacking a pharmacokinetic marker to understand the inter-individual differences in ICB response. ICB therapy is based on IgG antibodies that share the same homeostatic pathway with serum albumin. Ther...

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Autor principal: Zheng, Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9772729/
https://www.ncbi.nlm.nih.gov/pubmed/36600664
http://dx.doi.org/10.1136/jitc-2022-005670
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author Zheng, Ming
author_facet Zheng, Ming
author_sort Zheng, Ming
collection PubMed
description As we look forward to the bright future of immune checkpoint blockade (ICB) therapy, there is still lacking a pharmacokinetic marker to understand the inter-individual differences in ICB response. ICB therapy is based on IgG antibodies that share the same homeostatic pathway with serum albumin. Therefore, serum albumin level could reflect IgG catabolic rate that directly impacts the clearance of therapeutic IgG antibodies. Through interrogating a large, clinically representative pan-cancer cohort of 1,479 ICB-treated patients, this study found that higher baseline albumin levels were significantly associated with stepwise improvements in overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) (p<0.001), with the variability and reproducibility confirmed in 1,000 bootstrap-resampled cohorts. Furthermore, these findings were also confirmed in most subgroups defined by patient demographics, baseline characteristics, treatments, and cancer types, even in those with low ICB-responsive cancer types and low tumor mutation burden (TMB) (TMB≤10 mut/Mb) that most of which have not been approved by the US Food and Drug Administration (FDA) for ICB therapy. In summary, this study highlights the importance of pretreatment pharmacokinetic modeling for predicting ICB treatment outcomes. Based on serum albumin—an inexpensive, non-invasive, and easily accessible biomarker of IgG pharmacokinetics, we could take a step further towards optimizing ICB therapy.
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spelling pubmed-97727292022-12-23 Serum albumin: a pharmacokinetic marker for optimizing treatment outcome of immune checkpoint blockade Zheng, Ming J Immunother Cancer Hypothesis As we look forward to the bright future of immune checkpoint blockade (ICB) therapy, there is still lacking a pharmacokinetic marker to understand the inter-individual differences in ICB response. ICB therapy is based on IgG antibodies that share the same homeostatic pathway with serum albumin. Therefore, serum albumin level could reflect IgG catabolic rate that directly impacts the clearance of therapeutic IgG antibodies. Through interrogating a large, clinically representative pan-cancer cohort of 1,479 ICB-treated patients, this study found that higher baseline albumin levels were significantly associated with stepwise improvements in overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) (p<0.001), with the variability and reproducibility confirmed in 1,000 bootstrap-resampled cohorts. Furthermore, these findings were also confirmed in most subgroups defined by patient demographics, baseline characteristics, treatments, and cancer types, even in those with low ICB-responsive cancer types and low tumor mutation burden (TMB) (TMB≤10 mut/Mb) that most of which have not been approved by the US Food and Drug Administration (FDA) for ICB therapy. In summary, this study highlights the importance of pretreatment pharmacokinetic modeling for predicting ICB treatment outcomes. Based on serum albumin—an inexpensive, non-invasive, and easily accessible biomarker of IgG pharmacokinetics, we could take a step further towards optimizing ICB therapy. BMJ Publishing Group 2022-12-20 /pmc/articles/PMC9772729/ /pubmed/36600664 http://dx.doi.org/10.1136/jitc-2022-005670 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Hypothesis
Zheng, Ming
Serum albumin: a pharmacokinetic marker for optimizing treatment outcome of immune checkpoint blockade
title Serum albumin: a pharmacokinetic marker for optimizing treatment outcome of immune checkpoint blockade
title_full Serum albumin: a pharmacokinetic marker for optimizing treatment outcome of immune checkpoint blockade
title_fullStr Serum albumin: a pharmacokinetic marker for optimizing treatment outcome of immune checkpoint blockade
title_full_unstemmed Serum albumin: a pharmacokinetic marker for optimizing treatment outcome of immune checkpoint blockade
title_short Serum albumin: a pharmacokinetic marker for optimizing treatment outcome of immune checkpoint blockade
title_sort serum albumin: a pharmacokinetic marker for optimizing treatment outcome of immune checkpoint blockade
topic Hypothesis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9772729/
https://www.ncbi.nlm.nih.gov/pubmed/36600664
http://dx.doi.org/10.1136/jitc-2022-005670
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