Investigation on environmental factors contributing to bispecific antibody stability and the reversal of self-associated aggregates  

作　　者：Nattha Ingavat Nuruljannah Dzulkiflie Jia Min Liew Xinhui Wang Eunice Leong Han Ping Loh Say Kong Ng Yuansheng Yang Wei Zhang 

机构地区：[1]Downstream Processing Group,Bioprocessing Technology Institute,Agency for Science,Technology and Research(A*STAR),Singapore,Singapore [2]Animal Cell Bioprocessing Group,Bioprocessing Technology Institute,Agency for Science,Technology and Research(A*STAR),Singapore,Singapore [3]Cell Line Development Group,Bioprocessing Technology Institute,Agency for Science,Technology and Research(A*STAR),Singapore,Singapore

出　　处：《Bioresources and Bioprocessing》2024年第1期1084-1101,共18页生物资源与生物加工(英文)

基　　金：supported by Agency for Science,Technology,and Research(A*STAR)BMRC Central Research Fund.

摘　　要：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.

关 键 词：Bispecific antibody Fab-scFv STABILITY Reversible-self association Environmental factors 

分 类 号：O17[理学—数学]