Atezolizumab neutralizing assay development: a novel way of evaluating assay cutpoint after sample pretreatment
Abstract Atezolizumab, a biotherapeutic monoclonal antibody directed against PD-L1, has been shown to be efficacious in multiple oncology indications. In clinical trials, a subset of patients developed anti-atezolizumab antibodies, necessitating the development of a neutralizing antibody (NAb) assay...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SpringerOpen
2025-02-01
|
| Series: | AAPS Open |
| Online Access: | https://doi.org/10.1186/s41120-024-00105-z |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823861831881457664 |
|---|---|
| author | Rachel Melendez Jane Ruppel Cecilia Leddy Jenny Yang Ann Brady Yenny Webb-Vargas Jochen Brumm Lynn Kamen Yuan Song |
| author_facet | Rachel Melendez Jane Ruppel Cecilia Leddy Jenny Yang Ann Brady Yenny Webb-Vargas Jochen Brumm Lynn Kamen Yuan Song |
| author_sort | Rachel Melendez |
| collection | DOAJ |
| description | Abstract Atezolizumab, a biotherapeutic monoclonal antibody directed against PD-L1, has been shown to be efficacious in multiple oncology indications. In clinical trials, a subset of patients developed anti-atezolizumab antibodies, necessitating the development of a neutralizing antibody (NAb) assay. A bead-based sample pretreatment method was developed to reduce high levels of therapeutic in patient serum samples. Untreated sample variability is reduced by this sample pretreatment, based on this, a novel approach was taken for determining an appropriate assay decision threshold (cutpoint). The therapeutic was added to the samples to mimic typical patient samples. The resulting assay was successfully validated and applied to sample analysis from multiple clinical trials. |
| format | Article |
| id | doaj-art-a581aea90a2e4093bce917cfe85ab2c1 |
| institution | Kabale University |
| issn | 2364-9534 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | AAPS Open |
| spelling | doaj-art-a581aea90a2e4093bce917cfe85ab2c12025-02-09T12:47:08ZengSpringerOpenAAPS Open2364-95342025-02-0111111110.1186/s41120-024-00105-zAtezolizumab neutralizing assay development: a novel way of evaluating assay cutpoint after sample pretreatmentRachel Melendez0Jane Ruppel1Cecilia Leddy2Jenny Yang3Ann Brady4Yenny Webb-Vargas5Jochen Brumm6Lynn Kamen7Yuan Song8Bioanalytical Sciences, Genentech, IncBioanalytical Sciences, Genentech, IncBioanalytical Sciences, Genentech, IncBioanalytical Sciences, Genentech, IncBioanalytical Sciences, Genentech, IncBioanalytical Sciences, Genentech, IncData Science Statistical, gRED OncologyBioagilytixBioanalytical Sciences, Genentech, IncAbstract Atezolizumab, a biotherapeutic monoclonal antibody directed against PD-L1, has been shown to be efficacious in multiple oncology indications. In clinical trials, a subset of patients developed anti-atezolizumab antibodies, necessitating the development of a neutralizing antibody (NAb) assay. A bead-based sample pretreatment method was developed to reduce high levels of therapeutic in patient serum samples. Untreated sample variability is reduced by this sample pretreatment, based on this, a novel approach was taken for determining an appropriate assay decision threshold (cutpoint). The therapeutic was added to the samples to mimic typical patient samples. The resulting assay was successfully validated and applied to sample analysis from multiple clinical trials.https://doi.org/10.1186/s41120-024-00105-z |
| spellingShingle | Rachel Melendez Jane Ruppel Cecilia Leddy Jenny Yang Ann Brady Yenny Webb-Vargas Jochen Brumm Lynn Kamen Yuan Song Atezolizumab neutralizing assay development: a novel way of evaluating assay cutpoint after sample pretreatment AAPS Open |
| title | Atezolizumab neutralizing assay development: a novel way of evaluating assay cutpoint after sample pretreatment |
| title_full | Atezolizumab neutralizing assay development: a novel way of evaluating assay cutpoint after sample pretreatment |
| title_fullStr | Atezolizumab neutralizing assay development: a novel way of evaluating assay cutpoint after sample pretreatment |
| title_full_unstemmed | Atezolizumab neutralizing assay development: a novel way of evaluating assay cutpoint after sample pretreatment |
| title_short | Atezolizumab neutralizing assay development: a novel way of evaluating assay cutpoint after sample pretreatment |
| title_sort | atezolizumab neutralizing assay development a novel way of evaluating assay cutpoint after sample pretreatment |
| url | https://doi.org/10.1186/s41120-024-00105-z |
| work_keys_str_mv | AT rachelmelendez atezolizumabneutralizingassaydevelopmentanovelwayofevaluatingassaycutpointaftersamplepretreatment AT janeruppel atezolizumabneutralizingassaydevelopmentanovelwayofevaluatingassaycutpointaftersamplepretreatment AT cecilialeddy atezolizumabneutralizingassaydevelopmentanovelwayofevaluatingassaycutpointaftersamplepretreatment AT jennyyang atezolizumabneutralizingassaydevelopmentanovelwayofevaluatingassaycutpointaftersamplepretreatment AT annbrady atezolizumabneutralizingassaydevelopmentanovelwayofevaluatingassaycutpointaftersamplepretreatment AT yennywebbvargas atezolizumabneutralizingassaydevelopmentanovelwayofevaluatingassaycutpointaftersamplepretreatment AT jochenbrumm atezolizumabneutralizingassaydevelopmentanovelwayofevaluatingassaycutpointaftersamplepretreatment AT lynnkamen atezolizumabneutralizingassaydevelopmentanovelwayofevaluatingassaycutpointaftersamplepretreatment AT yuansong atezolizumabneutralizingassaydevelopmentanovelwayofevaluatingassaycutpointaftersamplepretreatment |