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Design and Efficacy of a Monovalent Bispecific PD-1/CTLA4 Antibody That Enhances CTLA4 Blockade on PD-1(+) Activated T Cells : Design and Efficacy of a Monovalent Bispecific PD-1/CTLA4 Antibody That Enhances CTLA4 Blockade on PD-1+ Activated T Cells
DC Field | Value | Language |
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dc.contributor.author | Dovedi, Simon J. | - |
dc.contributor.author | Elder, Matthew J. | - |
dc.contributor.author | Yang, Chunning | - |
dc.contributor.author | Sitnikova, Suzanne, I | - |
dc.contributor.author | Irving, Lorraine | - |
dc.contributor.author | Hansen, Anna | - |
dc.contributor.author | Hair, James | - |
dc.contributor.author | Jones, Des C. | - |
dc.contributor.author | Hasani, Sumati | - |
dc.contributor.author | Wang, Bo | - |
dc.contributor.author | Im, Seock-Ah | - |
dc.contributor.author | Ben Tran | - |
dc.contributor.author | Subramaniam, Deepa S. | - |
dc.contributor.author | Gainer, Shelby D. | - |
dc.contributor.author | Vashisht, Kapil | - |
dc.contributor.author | Lewis, Arthur | - |
dc.contributor.author | Jin, Xiaofang | - |
dc.contributor.author | Kentner, Stacy | - |
dc.contributor.author | Mulgrew, Kathy | - |
dc.contributor.author | Wang, Yaya | - |
dc.contributor.author | Overstreet, Michael G. | - |
dc.contributor.author | Dodgson, James | - |
dc.contributor.author | Wu, Yanli | - |
dc.contributor.author | Palazon, Asis | - |
dc.contributor.author | Morrow, Michelle | - |
dc.contributor.author | Rainey, Godfrey J. | - |
dc.contributor.author | Browne, Gareth J. | - |
dc.contributor.author | Neal, Frances | - |
dc.contributor.author | Murray, Thomas, V | - |
dc.contributor.author | Toloczko, Aleksandra D. | - |
dc.contributor.author | Dall'Acqua, William | - |
dc.contributor.author | Achour, Ikbel | - |
dc.contributor.author | Freeman, Daniel J. | - |
dc.contributor.author | Wilkinson, Robert W. | - |
dc.contributor.author | Mazor, Yariv | - |
dc.date.accessioned | 2022-03-22T09:11:28Z | - |
dc.date.available | 2022-03-22T09:11:28Z | - |
dc.date.created | 2021-06-08 | - |
dc.date.created | 2021-06-08 | - |
dc.date.created | 2021-06-08 | - |
dc.date.created | 2021-06-08 | - |
dc.date.issued | 2021-05 | - |
dc.identifier.citation | Cancer Discovery, Vol.11 No.5, pp.1100-1117 | - |
dc.identifier.issn | 2159-8274 | - |
dc.identifier.other | 134851 | - |
dc.identifier.uri | https://hdl.handle.net/10371/177231 | - |
dc.description.abstract | The clinical benefit of PD-1 blockade can be improved by combination with CTLA4 inhibition but is commensurate with significant immune-related adverse events suboptimally limiting the doses of anti-CTLA4 mAb that can be used. MEDI5752 is a monovalent bispecific antibody designed to suppress the PD-1 pathway and provide modulated CTLA4 inhibition favoring enhanced blockade on PD-1(+) activated T cells. We show that MEDI5752 preferentially saturates CTLA4 on PD-1(+) T cells versus PD-1(-) T cells, reducing the dose required to elicit IL2 secretion. Unlike conventional PD-1/CTLA4 mAbs, MEDI5752 leads to the rapid internalization and degradation of PD-1. Moreover, we show that MEDI5752 preferentially localizes and accumulates in tumors providing enhanced activity when compared with a combination of mAbs targeting PD-1 and CTLA4 in vivo. Following treatment with MEDI5752, robust partial responses were observed in two patients with advanced solid tumors. MEDI5752 represents a novel immunotherapy engineered to preferentially inhibit CTLA4 on PD-1(+) T cells. SIGNIFICANCE: The unique characteristics of MEDI5752 represent a novel immunotherapy engineered to direct CTLA4 inhibition to PD-1(+) T cells with the potential for differentiated activity when compared with current conventional mAb combination strategies targeting PD-1 and CTLA4. This molecule therefore represents a step forward in the rational design of cancer immunotherapy. | - |
dc.language | 영어 | - |
dc.publisher | American Association for Cancer Research Inc. | - |
dc.title | Design and Efficacy of a Monovalent Bispecific PD-1/CTLA4 Antibody That Enhances CTLA4 Blockade on PD-1(+) Activated T Cells | - |
dc.title.alternative | Design and Efficacy of a Monovalent Bispecific PD-1/CTLA4 Antibody That Enhances CTLA4 Blockade on PD-1+ Activated T Cells | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 임석아 | - |
dc.identifier.doi | 10.1158/2159-8290.CD-20-1445 | - |
dc.citation.journaltitle | Cancer Discovery | - |
dc.identifier.wosid | 000648516100026 | - |
dc.identifier.scopusid | 2-s2.0-85106050234 | - |
dc.citation.endpage | 1117 | - |
dc.citation.number | 5 | - |
dc.citation.startpage | 1100 | - |
dc.citation.volume | 11 | - |
dc.identifier.sci | 000648516100026 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Im, Seock-Ah | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | ARM BINDING-EFFICIENCY | - |
dc.subject.keywordPlus | ANTIGEN-EXPRESSION | - |
dc.subject.keywordPlus | MOLECULAR-BASIS | - |
dc.subject.keywordPlus | TUMOR | - |
dc.subject.keywordPlus | TARGET | - |
dc.subject.keywordPlus | COMBINATION | - |
dc.subject.keywordPlus | MONOTHERAPY | - |
dc.subject.keywordPlus | ENGAGEMENT | - |
dc.subject.keywordPlus | EFFECTOR | - |
dc.subject.keywordPlus | AFFINITY | - |
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