Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemERG-6333Cat.No.:HY-P991176Synonyms:RO7443904作?靶點(diǎn):CD19;CD28作?通路:Immunology/Inflammation儲(chǔ)存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性RG-6333?種靶向CD19和CD28的雙特異性激動(dòng)劑。RG-6333特異性識(shí)別并結(jié)合B細(xì)胞惡性腫瘤表的CD19抗原，定位腫瘤細(xì)胞。RG-6333通過(guò)與CD28結(jié)合激活T細(xì)胞，克服激活障礙，增強(qiáng)抗腫瘤免疫?。RG-6333能夠?于復(fù)發(fā)/難治性?霍奇?淋巴瘤的研究。推薦同型對(duì)照為humanIgG4kappa，同型對(duì)照(HY-P99003)[1][2]。體外研究RG-6333(RO7443904)hasaloweraffinityforCD28inCHOcells(Kd:36nM),bindingweaklybutsufficienttoprovideaco-stimulatorysignal[1].RG-6333isinactiveasasingleagentinhumanperipheralbloodmononuclearcells(PBMC)andactivatesTcellsonlyuponengagementoftheTcellreceptor(TCR)[1].體內(nèi)研究RG-6333(1,10mg/kg,i.v.onedose)activatesTcellsonlyinthepresenceofTcellreceptor(TCR)signalinginhumanizedNSGmiceanddoesnotinduceacytokinestorm[1][2].RG-6333(1mg/kg,i.v.onedose)significantlyinhibitstumorgrowthinhumanizedNSGmicebearingsubcutaneousNALM-6lymphomaincombinationwithGlofitamab(HY-P99024)(0.15mg/kg),andincreasestumor-infiltratingCD8+Tcells[1].RG-6333(1mg/kg,i.v.onedose)combineswithGlofitamab(0.15mg/kg)inanaggressiveinvivolymphoma(DLBCLWSU-DLCL2-Fluc)humanizedmicemodelresultsincompletetumorregression,withaninitialtransientweightlossduetoTcellactivation,butsubsequentrecovery[1][2].RG-6333(1mg/kg,i.v.onedose)combineswithglofitamab(0.15mg/kg)inahumanizedNSGmicemodelbearingsubcutaneousOCI-Ly18tumorsincreasespro-inflammatoryTcellsignaturesintumorsandpromotestransendothelialmigration,andtriplecombinationwithCD19–4-1BBLdeepensandprolongsanti-tumorresponsesinvivo[1].1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAnimalModel:HumanizedNSGmicebearingorthotopicWSU-DLCL2-Fluctumors[1]Dosage:1mg/kgAdministration:i.v.threetimescombinedinjectionResult:CombinedwithGlofitamab(0.15mg/kg)achievedcompletetumorregression,withinitialweightlossinmice,whichisrelatedtothemodeofactionofTCBanditsinducedcytokinerelease.CombinedwithGlofitamab(0.15mg/kg)ledtosubsequentrecoveryofmicewithoutadditionalweightlosssuggestiveoftumorprogression,indicatedpotentantitumoractivity.AnimalModel:OCI-Ly18tumor-bearinghumanizedNSGmice[1]Dosage:1mg/kgAdministration:i.v.threetimescombinedinjectionResult:CombinedwithGlofitamab(1mg/kg)increasedintratumoralCD8+andCD4+T-cellcounts.CombinedwithGlofitamab(1mg/kg)ledtoamarkedincreaseinIFNγpathwaygenes,followedbysignificantlyincreasedcytotoxicT-cellanddecreasedB-cellsignatures.CombinedwithGlofitamab(1mg/kg)andCD19-4-1BBL(1mg/kg)prolongedtheanti-tumorresponseinvivoandachievinglong-termtumorcontrol.REFERENCES[1].SamJ,etal.CD19-CD28:anaffinity-optimizedCD28agonistforcombinationwithglofitamab(CD20-TCB)asoff-the-shelfimmunotherapy.Blood.2024May23;143(21):2152-2165.[2].SamJ,etal.RG6333(CD19-CD28),aCD19-targetedaffinity-optimizedCD28bispecificantibody,enhancesandprolongstheanti-tumoractivityofglofitamab(CD20-TCB)inpreclinicalmodels.Blood140.Supplement1(2022):3142-3143.McePdfHeightCaution:Producthasnotbeenfu