Development and validation of a functional cell-based neutralizing antibody assay for ipilimumab-Reference-Cited by-同舟云学术

Development and validation of a functional cell-based neutralizing antibody assay for ipilimumab

Published:2018-08-01 Issue:16 Volume:10 Page:1273-1287
ISSN:1757-6180
Container-title:Bioanalysis
language:en
Short-container-title:Bioanalysis

Author:

Xu Weifeng¹,Cummings Jennifer¹,Sank Michael¹,Juhel Marina¹,Li Xuefeng¹²,Gleason Carol¹,DeSilva Binodh S¹,Dodge Robert W¹,Pillutla Renuka¹

Affiliation:

1. Analytical & Bioanalytical Operations, Bristol-Myers Squibb, Princeton, NJ 08543, USA

2. Current address: Innovent Biologics (Suzhou) Co. Ltd, 168 Dongping Street, Suzhou Industrial Park 215123, PR China

Abstract

Ipilimumab is the first US FDA-approved immune checkpoint-blocking antibody drug to harness the patient's own immune cells. One of the postmarketing requirements is to develop a cell-based neutralizing antibody assay. Here, we share some of the most challenging aspects encountered during the assay development: new cell line construction; an unexpected inhibition of T-cell activation by low concentrations of ipilimumab; and two issues caused by sample pretreatment with acid dissociation to overcome drug interference: instability of neutralizing antibody positive control at low pH, and incompatibility of commonly used acid dissociation buffers in the cell assay. After troubleshooting and optimization, we successfully validated the assay and used the assay to test clinical samples to date.

Publisher

Future Science Ltd

Subject

Medical Laboratory Technology,Clinical Biochemistry,General Pharmacology, Toxicology and Pharmaceutics,General Medicine,Analytical Chemistry

Link

http://www.future-science.com/doi/pdf/10.4155/bio-2018-0109

Reference33 articles.

1. CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation.

2. Immunologic Self-Tolerance Maintained by Cd25+Cd4+Regulatory T Cells Constitutively Expressing Cytotoxic T Lymphocyte–Associated Antigen 4

3. Enhancement of Antitumor Immunity by CTLA-4 Blockade

4. Improved Survival with Ipilimumab in Patients with Metastatic Melanoma

5. Cancer Immunotherapy

Cited by 10 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Development and Validation of a Cell-Based Binding Neutralizing Antibody Assay for an Antibody–Drug Conjugate;The AAPS Journal;2024-03-28

2. 2022 White Paper on Recent Issues in Bioanalysis: Enzyme Assay Validation, BAV for Primary End Points, Vaccine Functional Assays, Cytometry in Tissue, LBA in Rare Matrices, Complex NAb Assays, Spectral Cytometry, Endogenous Analytes, Extracellular Vesicles Part 2 – Recommendations on Biomarkers/CDx, Flow Cytometry, Ligand-Binding Assays Development & Validation; Emerging Technologies; Critical Reagents Deep Characterization;Bioanalysis;2023-08

3. Phage-derived anti-idiotype and anti-YTE antibodies in development of MK-1654 pharmacokinetic and immune response assays;Bioanalysis;2023-08

4. Development of a Cell-based Neutralizing Antibody Assay for Zinpentraxin Alfa: Challenges and Mitigation Strategies;The AAPS Journal;2023-07-20

5. A Novel Neutralization Antibody Assay Method to Overcome Drug Interference with Better Compatibility with Acid-Sensitive Neutralizing Antibodies;The AAPS Journal;2023-01-25