Investigation on Environmental Factors Contributing to Bispecific Antibody Stability and the Reversal of Self-associated Aggregates

Overview

Journal Bioresour Bioprocess

Specialty Biochemistry

Date 2024 Aug 23

PMID 39177850

Authors

Nattha Ingavat

Nuruljannah Dzulkiflie

Jia Min Liew

Xinhui Wang

Eunice Leong

Han Ping Loh

Say Kong Ng

Yuansheng Yang

Wei Zhang

Affiliations

Soon will be listed here.

Abstract

Bispecific antibodies (bsAbs) hold promises for enhanced therapeutic potential surpassing that of their parental monoclonal antibodies. However, bsAbs pose great challenges in their manufacturing, and one of the common reasons is their susceptibility to aggregation. Building on previous studies demonstrating the functionality and potential manufacturability of Fab-scFv format bsAb, this investigation delved into the impact of environmental factors-such as pH, buffer types, ionic strength, protein concentrations, and temperatures-on its stability and the reversal of its self-associated aggregates. Mildly acidic, low-salt conditions were found optimal, ensuring bsAb stability for 30 days even at elevated temperature of 40 °C. Furthermore, these conditions facilitated the reversal of its self-associated aggregates to monomers during the initial 7-day incubation period. Our findings underscore the robustness and resilience of Fab-scFv format bsAb, further confirming its potential manufacturability despite its current absence as commercial products.

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