Establishing endotoxin limits to enhance the reliability of in vitro immunogenicity risk assessments
Immunogenic responses to biotherapeutics often lead to termination of their development because the resulting anti-drug-antibodies (ADA) can negatively impact pharmacology, safety, and efficacy. To mitigate ADA risks, in vitro risk assessment assays in non-clinical settings are essential to enhance...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | mAbs |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19420862.2025.2458627 |
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| author | Yun Hee Jeong Gillian Lennon Geertruida Veldman Daniel M. Serna Alexander Ibrahimov |
| author_facet | Yun Hee Jeong Gillian Lennon Geertruida Veldman Daniel M. Serna Alexander Ibrahimov |
| author_sort | Yun Hee Jeong |
| collection | DOAJ |
| description | Immunogenic responses to biotherapeutics often lead to termination of their development because the resulting anti-drug-antibodies (ADA) can negatively impact pharmacology, safety, and efficacy. To mitigate ADA risks, in vitro risk assessment assays in non-clinical settings are essential to enhance safety and efficacy of protein-based therapeutics. This study aimed to develop and validate a human in vitro immunogenicity T cell proliferation assay. However, there is a lack of comprehensive guidelines for managing product-related factors such as endotoxin contamination, which can significantly influence assay sensitivity and accuracy. Our investigation of the impact of endotoxins revealed that levels above 0.1 EU/mg significantly induce T cell proliferation and CD14+ myeloid cell expansion, leading to potential false-positive outcomes in immunogenicity assessments. These findings suggest the importance of developing standardized protocols to enhance the predictive capability of in vitro methods, ensuring the assessment of therapeutic proteins accurately reflects their immunogenic potential without interference from contaminants. |
| format | Article |
| id | doaj-art-3c606ba075ff48eab03c07196423fb15 |
| institution | Kabale University |
| issn | 1942-0862 1942-0870 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | mAbs |
| spelling | doaj-art-3c606ba075ff48eab03c07196423fb152025-02-02T06:06:38ZengTaylor & Francis GroupmAbs1942-08621942-08702025-12-0117110.1080/19420862.2025.2458627Establishing endotoxin limits to enhance the reliability of in vitro immunogenicity risk assessmentsYun Hee Jeong0Gillian Lennon1Geertruida Veldman2Daniel M. Serna3Alexander Ibrahimov4In Vitro Immunosafety, Development Biological Sciences, Abbvie Bioresearch Center, Worcester, MA, USAIn Vitro Immunosafety, Development Biological Sciences, Abbvie Bioresearch Center, Worcester, MA, USABiotherapeutics Discovery Research, AbbVie Bioresearch Center, AbbVie Bioresearch Center, Worcester, MA, USAIn Vitro Immunosafety, Development Biological Sciences, Abbvie Bioresearch Center, Worcester, MA, USAIn Vitro Immunosafety, Development Biological Sciences, Abbvie Bioresearch Center, Worcester, MA, USAImmunogenic responses to biotherapeutics often lead to termination of their development because the resulting anti-drug-antibodies (ADA) can negatively impact pharmacology, safety, and efficacy. To mitigate ADA risks, in vitro risk assessment assays in non-clinical settings are essential to enhance safety and efficacy of protein-based therapeutics. This study aimed to develop and validate a human in vitro immunogenicity T cell proliferation assay. However, there is a lack of comprehensive guidelines for managing product-related factors such as endotoxin contamination, which can significantly influence assay sensitivity and accuracy. Our investigation of the impact of endotoxins revealed that levels above 0.1 EU/mg significantly induce T cell proliferation and CD14+ myeloid cell expansion, leading to potential false-positive outcomes in immunogenicity assessments. These findings suggest the importance of developing standardized protocols to enhance the predictive capability of in vitro methods, ensuring the assessment of therapeutic proteins accurately reflects their immunogenic potential without interference from contaminants.https://www.tandfonline.com/doi/10.1080/19420862.2025.2458627Endotoxinin vitro assayimmunogenicity risk assessmentT cell proliferation |
| spellingShingle | Yun Hee Jeong Gillian Lennon Geertruida Veldman Daniel M. Serna Alexander Ibrahimov Establishing endotoxin limits to enhance the reliability of in vitro immunogenicity risk assessments mAbs Endotoxin in vitro assay immunogenicity risk assessment T cell proliferation |
| title | Establishing endotoxin limits to enhance the reliability of in vitro immunogenicity risk assessments |
| title_full | Establishing endotoxin limits to enhance the reliability of in vitro immunogenicity risk assessments |
| title_fullStr | Establishing endotoxin limits to enhance the reliability of in vitro immunogenicity risk assessments |
| title_full_unstemmed | Establishing endotoxin limits to enhance the reliability of in vitro immunogenicity risk assessments |
| title_short | Establishing endotoxin limits to enhance the reliability of in vitro immunogenicity risk assessments |
| title_sort | establishing endotoxin limits to enhance the reliability of in vitro immunogenicity risk assessments |
| topic | Endotoxin in vitro assay immunogenicity risk assessment T cell proliferation |
| url | https://www.tandfonline.com/doi/10.1080/19420862.2025.2458627 |
| work_keys_str_mv | AT yunheejeong establishingendotoxinlimitstoenhancethereliabilityofinvitroimmunogenicityriskassessments AT gillianlennon establishingendotoxinlimitstoenhancethereliabilityofinvitroimmunogenicityriskassessments AT geertruidaveldman establishingendotoxinlimitstoenhancethereliabilityofinvitroimmunogenicityriskassessments AT danielmserna establishingendotoxinlimitstoenhancethereliabilityofinvitroimmunogenicityriskassessments AT alexanderibrahimov establishingendotoxinlimitstoenhancethereliabilityofinvitroimmunogenicityriskassessments |