DC Field | Value | Language |
---|---|---|
dc.contributor.author | Jang, Seil | ko |
dc.contributor.author | Song, Jaeho | ko |
dc.contributor.author | Kim, NaYoung | ko |
dc.contributor.author | Bak, Jeonghyeon | ko |
dc.contributor.author | Jung, Keehoon | ko |
dc.contributor.author | Park, Young Woo | ko |
dc.contributor.author | Park, Bum-Chan | ko |
dc.contributor.author | Kim, Ho Min | ko |
dc.date.accessioned | 2021-05-18T01:10:10Z | - |
dc.date.available | 2021-05-18T01:10:10Z | - |
dc.date.created | 2021-05-17 | - |
dc.date.created | 2021-05-17 | - |
dc.date.created | 2021-05-17 | - |
dc.date.created | 2021-05-17 | - |
dc.date.created | 2021-05-17 | - |
dc.date.issued | 2021-04 | - |
dc.identifier.citation | BIOMATERIALS, v.271 | - |
dc.identifier.issn | 0142-9612 | - |
dc.identifier.uri | http://hdl.handle.net/10203/285270 | - |
dc.description.abstract | Following the clinical success of immunotherapeutic antibodies, bispecific antibodies for cytotoxic effector cell redirection, tumor-targeted immunomodulation and dual immunomodulation, have received particular attentions. Here, we developed a novel bispecific antibody platform, termed Antibody-Like Cell Engager (ALiCE), wherein the Fc domain of each heavy chain of immunoglobulin G (IgG) is replaced by the VH and VL domains of an IgG specific to a second antigen while retaining the N-terminal Fab of the parent antibody. Because of specific interactions between the substituted VH and VL domains, the C-terminal stem Fv enables ALiCE to assemble autonomously into hetero-tetramers, thus simultaneously binding to two distinct antigens but with different avidities. This design strategy was used to generate ACE-05 (two anti-PD-L1 Fab × anti-CD3 Fv) and ACE-31 (two anti-CD3 Fab × anti-PD-L1 Fv), both of which bound PD-L1 and CD3. However, ACE-05 was more effective than ACE-31 in reducing off-target toxicity caused by the indiscriminate activation of T cells. Moreover, in cell-based assays and PBMC-reconstituted humanized mice harboring human non-small-cell lung cancer tumors, ACE-05 showed marked antitumor efficacy, causing complete tumor regression at a dose of 0.05 mg/kg body weight. The dual roles of ACE-05 in immune checkpoint inhibition and T-cell redirection, coupled with reduced off-target toxicity, suggest that ACE-05 may be a promising anti-cancer therapeutic agent. Moreover, the bispecific ALiCE platform can be further used for tumor-targeted or multiple immunomodulation applications. | - |
dc.language | English | - |
dc.publisher | ELSEVIER SCI LTD | - |
dc.title | Development of an antibody-like T-cell engager based on VH-VL heterodimer formation and its application in cancer therapy | - |
dc.type | Article | - |
dc.identifier.wosid | 000639774500002 | - |
dc.identifier.scopusid | 2-s2.0-85103125760 | - |
dc.type.rims | ART | - |
dc.citation.volume | 271 | - |
dc.citation.publicationname | BIOMATERIALS | - |
dc.identifier.doi | 10.1016/j.biomaterials.2021.120760 | - |
dc.contributor.localauthor | Kim, Ho Min | - |
dc.contributor.nonIdAuthor | Song, Jaeho | - |
dc.contributor.nonIdAuthor | Kim, NaYoung | - |
dc.contributor.nonIdAuthor | Bak, Jeonghyeon | - |
dc.contributor.nonIdAuthor | Jung, Keehoon | - |
dc.contributor.nonIdAuthor | Park, Young Woo | - |
dc.contributor.nonIdAuthor | Park, Bum-Chan | - |
dc.description.isOpenAccess | Y | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | Antibody-engineering | - |
dc.subject.keywordAuthor | Bispecific antibody | - |
dc.subject.keywordAuthor | T-cell engager | - |
dc.subject.keywordAuthor | Cancer immunotherapy | - |
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