About: Next generation of anti-PD-L1 Atezolizumab with better anti-tumor efficacy in vivo

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About: Next generation of anti-PD-L1 Atezolizumab with better anti-tumor efficacy in vivo Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Next generation of anti-PD-L1 Atezolizumab with better anti-tumor efficacy in vivo
Creator	Li, Song Chen, Jianxin Li, Maohua Ren, Wenlin Sun, Hunter Sun, Le Xia, Chenxi Zhao, Rongqing Li, Yingzi Liu, Xudong Shen, Tong Tian, Wenzhi Yan, Yuyuan
source	BioRxiv
abstract	Some cancer patients treated with Atezolizumab, PD-L1 antibody drug launched by Genentech, quickly developed anti-drug antibody (ADA), led to loss of efficacy. This was likely due to the heavy aggregation of Atezolizumab, caused by mutation of N297A for removing unwanted antibody-dependent cytotoxicity (ADCC) of IgG1 antibody drug. Here, we developed a new version of Atezolizumab (Maxatezo), which was demonstrated better anti-tumor efficacy in vivo. In Atezolizumab, we mutated 297A to 297N back to bring back the glycosylation, and inserted a short sequence GGGS between G237 and G238 in the hinge region of the IgG1 heavy chain. Our data shown that insertion of GGGS, without altering the anti-PD-L1 antibody affinity and inhibitory activity, completely abolished the ADCC activity, as same as Atezolizumab. Moreover, the insertion of GGGS, without altering the glycosylation profile of IgG1, increased the yields of anti-PD-L1 antibody considerately. Additionally, glycosylation improved the stability yet reduced the amounts of aggregations in the antibody solutions. In turn, the level of ADA in animals treated with Maxatezo was 70% lower than the ones treated with Atezolizumab. Most importantly, at the same 10mg/kg dose, the anti-tumor activity of Maxatezo had attained 98% compared to that of Atezolizumab at 68%.
has issue date	2020-07-01(xsd:dateTime)
bibo:doi	10.1101/2020.06.30.166207
has license	biorxiv
sha1sum (hex)	7bde6d78f3eab9f446ccc6d2eec18e68db552ec1
schema:url	https://doi.org/10.1101/2020.06.30.166207
resource representing a document's title	Next generation of anti-PD-L1 Atezolizumab with better anti-tumor efficacy in vivo
schema:publication	bioRxiv
resource representing a document's body	covid:7bde6d78f3eab9f446ccc6d2eec18e68db552ec1#body_text
is schema:about of	named entity 'developed' named entity 'antibody' named entity 'completely' named entity 'Atezolizumab' named entity 'HINGE' named entity 'INSERTION' named entity 'TUMOR' named entity 'HEAVY' named entity 'ANTI-DRUG ANTIBODY' named entity 'SHORT' named entity 'TREATED WITH' named entity 'PD-L1' named entity 'INSERTED' named entity 'LIKELY' named entity 'NEW' named entity 'IgG1' named entity 'mice' named entity 'antibody' named entity 'tumor' named entity 'antigen' named entity 'tumors' named entity 'Monomers' named entity 'antibodies' named entity 'Atezolizumab' named entity 'tumor cells' named entity 'CDC' named entity 'ADCC' named entity 'antibody' named entity 'glycan' named entity 'antibodies' named entity 'cytokines' named entity 'antibody' named entity 'tumor growth' named entity 'alveolar macrophages' named entity 'Balb/c' named entity 'fluorescence detector' named entity 'specific antigens' named entity 'antibody' named entity 'Assay' named entity 'NK cells' named entity 'test subject' named entity 'anti-drug' named entity 'IgG1' named entity 'binding sites' named entity 'HMW' named entity 'FcγRI' named entity 'mechanisms of action' named entity 'glycan' named entity 'receptor' named entity 'antibody' named entity 'Atezolizumab' named entity 'antibodies' named entity 'secretion' named entity 'Phase III' named entity 'IgG1' named entity 'expression levels' named entity 'HPLC' named entity 'fluorescence' named entity 'antibody' named entity 'PD-1' named entity 'Atezolizumab' named entity 'mice' named entity 'FcγRIIIA' named entity 'PBS' named entity 'CHO' named entity 'protein' named entity 'antigen' named entity 'rational design' named entity 'Balb/c' named entity 'dose-dependent manner' named entity 'Immunogenicity' named entity 'antibody'

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