FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4310112816> ?p ?o ?g. }

• W4310112816 endingPage "11559" @default.
• W4310112816 startingPage "11559" @default.
• W4310112816 abstract "CD20 is expressed by >90% of B-cell non-Hodgkin's lymphomas (NHL). Several generations of CD20-targeting monoclonal antibodies including rituximab, ofatumumab, and obinutuzumab have been widely used for B-cell malignancy therapies. Despite the recent approvals of novel CD20-targeting agents, new alternatives and strategies are still required for patients, which are relapsing or refractory after several lines of treatment. High circulating NK cell numbers have been associated with better clinical responses to anti-CD20- targeting monoclonal antibodies, supporting the role of NK cells in efficacy of these treatments. IPH6501, a novel antibody-based NK cell engager therapeutics (ANKET), is a single tetraspecific molecule engaging two NK cell activating receptors NKp46 and CD16a (FcγRIIIa), the β chain (CD122) of the interleukin-2 receptor (IL-2R), and the CD20 antigen expressed on malignant B cells. The IL-2R binding element incorporated in IPH6501 is an IL-2 variant (IL-2v) designed with point mutations that abolish binding to the IL-2R-α chain (CD25), with the goal of limiting toxicity and interaction with Tregs. IL-2v incorporated into IPH6501 is directed towards NK cells through the binding with high affinity to NKp46 and CD16a, providing its ability to interact with IL-2R preferentially on NK cells and to promote their activation and proliferation at pM doses. IPH6501 was designed to induce NK cell mediated-cytotoxicity and cytokine secretion by co-engaging CD16a and NKp46. Only the binding of IPH6501 to CD20, bridging the NK cells to the target cells, was able to trigger the cytotoxic activity of NK cells. Non-saturating doses of IPH6501 on NK cells and on CD20+ cells were sufficient to promote maximal killing activity. Furthermore, IPH6501 promoted NK cell cytotoxicity against tumor cells expressing very low levels of CD20. IPH6501 also demonstrated superiority to control tumor cell growth in vitro, as compared to the CD20-targeting clinical benchmark antibodies rituximab and the Fc-optimized obinutuzumab. In vivo treatment with a mouse surrogate of IPH6501 induced peripheral NK cell proliferation and activation, and demonstrated potent antitumor efficacy in a xenograft mouse model using the aggressive human B-lymphoma CD20+ RAJI cell line engrafted subcutaneously. In non-human primate, a well-tolerated dose of IPH6501 led to peripheral NK cell expansion and to the depletion of CD20+ B cells in the circulation and within lymphoid tissues, with minimal systemic cytokine release. In conclusion, IPH6501 is a first-in-class CD20-targeting tetraspecific NK cell engager designed to promote NK cell proliferation and specific cytotoxicity against CD20+ cells. IPH6501 is thus a promising biologic designed to harness the anti-tumor functions of NK cells in CD20+ B cell malignancies. IND-enabling studies are ongoing, and IPH6501 is expected to enter FIH clinical study in 2023." @default.
• W4310112816 created "2022-11-30" @default.
• W4310112816 creator A5035681124 @default.
• W4310112816 creator A5036943577 @default.
• W4310112816 creator A5039329858 @default.
• W4310112816 creator A5040855526 @default.
• W4310112816 creator A5045545522 @default.
• W4310112816 creator A5048040256 @default.
• W4310112816 creator A5051292571 @default.
• W4310112816 creator A5052780227 @default.
• W4310112816 creator A5061135039 @default.
• W4310112816 creator A5064976704 @default.
• W4310112816 creator A5080932104 @default.
• W4310112816 creator A5090256483 @default.
• W4310112816 date "2022-11-15" @default.
• W4310112816 modified "2023-10-01" @default.
• W4310112816 title "IPH6501 Is a Novel NKp46-Targeting Tetraspecific Antibody-Based Natural Killer Cell Engager Therapeutic (ANKET) Armed with a Non-Alpha IL-2 Variant and Developed for the Treatment of CD20-Positive Malignancies" @default.
• W4310112816 doi "https://doi.org/10.1182/blood-2022-163561" @default.
• W4310112816 hasPublicationYear "2022" @default.
• W4310112816 type Work @default.
• W4310112816 citedByCount "1" @default.
• W4310112816 countsByYear W43101128162023 @default.
• W4310112816 crossrefType "journal-article" @default.
• W4310112816 hasAuthorship W4310112816A5035681124 @default.
• W4310112816 hasAuthorship W4310112816A5036943577 @default.
• W4310112816 hasAuthorship W4310112816A5039329858 @default.
• W4310112816 hasAuthorship W4310112816A5040855526 @default.
• W4310112816 hasAuthorship W4310112816A5045545522 @default.
• W4310112816 hasAuthorship W4310112816A5048040256 @default.
• W4310112816 hasAuthorship W4310112816A5051292571 @default.
• W4310112816 hasAuthorship W4310112816A5052780227 @default.
• W4310112816 hasAuthorship W4310112816A5061135039 @default.
• W4310112816 hasAuthorship W4310112816A5064976704 @default.
• W4310112816 hasAuthorship W4310112816A5080932104 @default.
• W4310112816 hasAuthorship W4310112816A5090256483 @default.
• W4310112816 hasBestOaLocation W43101128161 @default.
• W4310112816 hasConcept C159654299 @default.
• W4310112816 hasConcept C18031839 @default.
• W4310112816 hasConcept C203014093 @default.
• W4310112816 hasConcept C502942594 @default.
• W4310112816 hasConcept C71924100 @default.
• W4310112816 hasConceptScore W4310112816C159654299 @default.
• W4310112816 hasConceptScore W4310112816C18031839 @default.
• W4310112816 hasConceptScore W4310112816C203014093 @default.
• W4310112816 hasConceptScore W4310112816C502942594 @default.
• W4310112816 hasConceptScore W4310112816C71924100 @default.
• W4310112816 hasIssue "Supplement 1" @default.
• W4310112816 hasLocation W43101128161 @default.
• W4310112816 hasLocation W43101128162 @default.
• W4310112816 hasOpenAccess W4310112816 @default.
• W4310112816 hasPrimaryLocation W43101128161 @default.
• W4310112816 hasRelatedWork W1668678514 @default.
• W4310112816 hasRelatedWork W1995617640 @default.
• W4310112816 hasRelatedWork W2046904578 @default.
• W4310112816 hasRelatedWork W2084801194 @default.
• W4310112816 hasRelatedWork W2099244599 @default.
• W4310112816 hasRelatedWork W2102440256 @default.
• W4310112816 hasRelatedWork W2169024102 @default.
• W4310112816 hasRelatedWork W2400126894 @default.
• W4310112816 hasRelatedWork W2403537506 @default.
• W4310112816 hasRelatedWork W2801343089 @default.
• W4310112816 hasVolume "140" @default.
• W4310112816 isParatext "false" @default.
• W4310112816 isRetracted "false" @default.
• W4310112816 workType "article" @default.