FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4220768287> ?p ?o ?g. }

• W4220768287 abstract "Treatment of Diffuse Large B Cell Lymphoma (DLBCL) patients with rituximab and the CHOP treatment regimen is associated with frequent intrinsic and acquired resistance. However, treatment with a CD47 monoclonal antibody in combination with rituximab yielded high objective response rates in patients with relapsed/refractory DLBCL in a phase I trial. Here, we report on a new bispecific and fully human fusion protein comprising the extracellular domains of SIRPα and 4-1BBL, termed DSP107, for the treatment of DLBCL. DSP107 blocks the CD47:SIRPα 'don't eat me' signaling axis on phagocytes and promotes innate anticancer immunity. At the same time, CD47-specific binding of DSP107 enables activation of the costimulatory receptor 4-1BB on activated T cells, thereby, augmenting anticancer T cell immunity.Using macrophages, polymorphonuclear neutrophils (PMNs), and T cells of healthy donors and DLBCL patients, DSP107-mediated reactivation of immune cells against B cell lymphoma cell lines and primary patient-derived blasts was studied with phagocytosis assays, T cell activation and cytotoxicity assays. DSP107 anticancer activity was further evaluated in a DLBCL xenograft mouse model and safety was evaluated in cynomolgus monkey.Treatment with DSP107 alone or in combination with rituximab significantly increased macrophage- and PMN-mediated phagocytosis and trogocytosis, respectively, of DLBCL cell lines and primary patient-derived blasts. Further, prolonged treatment of in vitro macrophage/cancer cell co-cultures with DSP107 and rituximab decreased cancer cell number by up to 85%. DSP107 treatment activated 4-1BB-mediated costimulatory signaling by HT1080.4-1BB reporter cells, which was strictly dependent on the SIRPα-mediated binding of DSP107 to CD47. In mixed cultures with CD47-expressing cancer cells, DSP107 augmented T cell cytotoxicity in vitro in an effector-to-target ratio-dependent manner. In mice with established SUDHL6 xenografts, the treatment with human PBMCs and DSP107 strongly reduced tumor size compared to treatment with PBMCs alone and increased the number of tumor-infiltrated T cells. Finally, DSP107 had an excellent safety profile in cynomolgus monkeys.DSP107 effectively (re)activated innate and adaptive anticancer immune responses and may be of therapeutic use alone and in combination with rituximab for the treatment of DLBCL patients." @default.
• W4220768287 created "2022-04-03" @default.
• W4220768287 creator A5003376522 @default.
• W4220768287 creator A5003525771 @default.
• W4220768287 creator A5007939778 @default.
• W4220768287 creator A5016092997 @default.
• W4220768287 creator A5023702941 @default.
• W4220768287 creator A5025452461 @default.
• W4220768287 creator A5026196982 @default.
• W4220768287 creator A5029207595 @default.
• W4220768287 creator A5029566173 @default.
• W4220768287 creator A5033586033 @default.
• W4220768287 creator A5039068778 @default.
• W4220768287 creator A5041782447 @default.
• W4220768287 creator A5041985338 @default.
• W4220768287 creator A5043125083 @default.
• W4220768287 creator A5051104404 @default.
• W4220768287 creator A5053920607 @default.
• W4220768287 creator A5059735911 @default.
• W4220768287 creator A5061358677 @default.
• W4220768287 creator A5072325478 @default.
• W4220768287 creator A5072991940 @default.
• W4220768287 creator A5073806204 @default.
• W4220768287 creator A5085454892 @default.
• W4220768287 creator A5087435504 @default.
• W4220768287 date "2022-03-14" @default.
• W4220768287 modified "2023-10-14" @default.
• W4220768287 title "DSP107 combines inhibition of CD47/SIRPα axis with activation of 4-1BB to trigger anticancer immunity" @default.
• W4220768287 cites W1512799118 @default.
• W4220768287 cites W1793898094 @default.
• W4220768287 cites W1920011500 @default.
• W4220768287 cites W2068052762 @default.
• W4220768287 cites W2074801788 @default.
• W4220768287 cites W2094901950 @default.
• W4220768287 cites W2097733789 @default.
• W4220768287 cites W2106294189 @default.
• W4220768287 cites W2106545303 @default.
• W4220768287 cites W2133346943 @default.
• W4220768287 cites W2155959680 @default.
• W4220768287 cites W2205886515 @default.
• W4220768287 cites W2526887159 @default.
• W4220768287 cites W2550646651 @default.
• W4220768287 cites W2570685768 @default.
• W4220768287 cites W2744261860 @default.
• W4220768287 cites W2767731416 @default.
• W4220768287 cites W2770192040 @default.
• W4220768287 cites W2782076004 @default.
• W4220768287 cites W2797968236 @default.
• W4220768287 cites W2801302797 @default.
• W4220768287 cites W2802794587 @default.
• W4220768287 cites W2883863118 @default.
• W4220768287 cites W2899044337 @default.
• W4220768287 cites W2900183473 @default.
• W4220768287 cites W2911509876 @default.
• W4220768287 cites W2919758335 @default.
• W4220768287 cites W2920905579 @default.
• W4220768287 cites W2921760704 @default.
• W4220768287 cites W2939258716 @default.
• W4220768287 cites W2939955202 @default.
• W4220768287 cites W2950984691 @default.
• W4220768287 cites W2953880924 @default.
• W4220768287 cites W2968195194 @default.
• W4220768287 cites W2979899581 @default.
• W4220768287 cites W2982452225 @default.
• W4220768287 cites W2983474673 @default.
• W4220768287 cites W2998158139 @default.
• W4220768287 cites W3009534977 @default.
• W4220768287 cites W3018840854 @default.
• W4220768287 cites W3020126301 @default.
• W4220768287 cites W3038831895 @default.
• W4220768287 cites W3097477684 @default.
• W4220768287 cites W3156547118 @default.
• W4220768287 doi "https://doi.org/10.1186/s13046-022-02256-x" @default.
• W4220768287 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35287686" @default.
• W4220768287 hasPublicationYear "2022" @default.
• W4220768287 type Work @default.
• W4220768287 citedByCount "10" @default.
• W4220768287 countsByYear W42207682872022 @default.
• W4220768287 countsByYear W42207682872023 @default.
• W4220768287 crossrefType "journal-article" @default.
• W4220768287 hasAuthorship W4220768287A5003376522 @default.
• W4220768287 hasAuthorship W4220768287A5003525771 @default.
• W4220768287 hasAuthorship W4220768287A5007939778 @default.
• W4220768287 hasAuthorship W4220768287A5016092997 @default.
• W4220768287 hasAuthorship W4220768287A5023702941 @default.
• W4220768287 hasAuthorship W4220768287A5025452461 @default.
• W4220768287 hasAuthorship W4220768287A5026196982 @default.
• W4220768287 hasAuthorship W4220768287A5029207595 @default.
• W4220768287 hasAuthorship W4220768287A5029566173 @default.
• W4220768287 hasAuthorship W4220768287A5033586033 @default.
• W4220768287 hasAuthorship W4220768287A5039068778 @default.
• W4220768287 hasAuthorship W4220768287A5041782447 @default.
• W4220768287 hasAuthorship W4220768287A5041985338 @default.
• W4220768287 hasAuthorship W4220768287A5043125083 @default.
• W4220768287 hasAuthorship W4220768287A5051104404 @default.
• W4220768287 hasAuthorship W4220768287A5053920607 @default.
• W4220768287 hasAuthorship W4220768287A5059735911 @default.
• W4220768287 hasAuthorship W4220768287A5061358677 @default.
• W4220768287 hasAuthorship W4220768287A5072325478 @default.
• W4220768287 hasAuthorship W4220768287A5072991940 @default.

• next