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...
Saved in:
| Main Author: | |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2022-12-01
|
| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/10/12/e005670.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846159127722590208 |
|---|---|
| author | Ming Zheng |
| author_facet | Ming Zheng |
| author_sort | Ming Zheng |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-b4c24191309b4a2c9d9dac7cc52e9e09 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-b4c24191309b4a2c9d9dac7cc52e9e092024-11-24T04:00:09ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262022-12-01101210.1136/jitc-2022-005670Serum albumin: a pharmacokinetic marker for optimizing treatment outcome of immune checkpoint blockadeMing Zheng0Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, Beijing, ChinaAs 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.https://jitc.bmj.com/content/10/12/e005670.full |
| spellingShingle | Ming Zheng Serum albumin: a pharmacokinetic marker for optimizing treatment outcome of immune checkpoint blockade Journal for ImmunoTherapy of Cancer |
| 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 |
| url | https://jitc.bmj.com/content/10/12/e005670.full |
| work_keys_str_mv | AT mingzheng serumalbuminapharmacokineticmarkerforoptimizingtreatmentoutcomeofimmunecheckpointblockade |