PCD Regulated Immunogenicity and Molecular, Merck and Co., Inc., West Point, PA 19486, USA.
Current address: Janssen Pharmaceutical, Ambler, PA 19002, USA.
Bioanalysis. 2023 Aug;15(16):1049-1067. doi: 10.4155/bio-2023-0081. Epub 2023 Jul 29.
MK-1654 is a fully human monoclonal antibody with YTE mutations currently in phase III clinical trials for prophylactic use in protecting infants from human respiratory syncytial virus infection. We generated anti-idiotype (anti-ID) and anti-YTE antibodies against MK-1654 by panning with MorphoSys HuCal phage libraries, and used the antibodies in the development of MK-1654 pharmacokinetic (PK) and immune response (IR) assays. Detection of MK-1654 in nonhuman primate and human nasal wash samples showed combined use of anti-ID and anti-YTE antibodies can deliver desired sensitivity and accuracy in PK studies. IR studies showed anti-ID can serve as suitable positive control in neutralizing antibody assays. Phage-derived anti-IDs and anti-YTEs are suitable for PK and IR assays.
MK-1654 是一种完全人源化单克隆抗体，带有 YTE 突变，目前正处于 III 期临床试验阶段，用于预防人类呼吸道合胞病毒感染。我们通过用 MorphoSys HuCal 噬菌体文库进行淘选，生成了针对 MK-1654 的抗独特型（anti-ID）和抗 YTE 抗体，并将这些抗体用于开发 MK-1654 的药代动力学（PK）和免疫反应（IR）检测。在非人类灵长类动物和人类鼻腔冲洗样本中的 MK-1654 检测结果表明，抗 ID 和抗 YTE 抗体的联合使用可在 PK 研究中提供所需的灵敏度和准确性。IR 研究表明，抗 ID 可作为中和抗体检测中的合适阳性对照。噬菌体衍生的抗 ID 和抗 YTE 可用于 PK 和 IR 检测。
