Update: new CD antigens, 1996

Kishimoto, Tadamitsu; Goyert, Sanna M.; Kikutani, Hitoshi; Mason, Donald M.; Miyasaka, M; Moretta, L; Ohno, Tomoyuki; Okumura, K; Shaw, S; Ta, Springer; Sugamura, Kazuo; Sugawara, Hiroyuki; Borne, von dem; Zola, Heddy

doi:10.1111/j.1399-0039.1997.tb02755.x

Cited by 5 publications

(1 citation statement)

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“…Briefly, liver tissues were processed to FFPE and sectioned as described in earlier studies [ 14 ]. FFPE sections were deparaffinized and rehydrated prior to immunofluorescent staining to detect BsAb-1 or BsAb-2, as well as endothelial cells (CD31 marker) [ 22 , 23 ]. Antigen retrieval was performed using the epitope retrieval solution, Diva Decloaker (BioCare Medical, Concord, CA, USA) for 30 s at 125 °C under pressure as reported in earlier studies [ 14 ].…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetic Developability and Disposition Profiles of Bispecific Antibodies: A Case Study with Two Molecules

et al. 2021

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Bispecific antibodies (BsAb) that engage multiple pathways are a promising therapeutic strategy to improve and prolong the efficacy of biologics in complex diseases. In the early stages of discovery, BsAbs often exhibit a broad range of pharmacokinetic (PK) behavior. Optimization of the neonatal Fc receptor (FcRn) interactions and removal of undesirable physiochemical properties have been used to improve the ‘pharmacokinetic developability’ for various monoclonal antibody (mAb) therapeutics, yet there is a sparsity of such information for BsAbs. The present work evaluated the influence of FcRn interactions and inherent physiochemical properties on the PK of two related single chain variable fragment (scFv)-based BsAbs. Despite their close relation, the two BsAbs exhibit disparate PK in cynomolgus monkeys with BsAb-1 having an aberrant clearance of ~2 mL/h/kg and BsAb-2 displaying a an ~10-fold slower clearance (~0.2 mL/h/kg). Evaluation of the physiochemical characteristics of the molecules, including charge, non-specific binding, thermal stability, and hydrophobic properties, as well as FcRn interactions showed some differences. In-depth drug disposition results revealed that a substantial disparity in the complete release from FcRn at a neutral pH is a primary factor contributing to the rapid clearance of the BsAb-1 while other biophysical characteristics were largely comparable between molecules.

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