二十、生物治疗药物推介与应用 编号：YZ20

项目简介：
Improvementofdiagnosticandtherapeuticstrategytocancerandcardiovasculardisease

:Productionofrecombinantsingleheavychaindomainantibodywithhighaffinityandspecificity
Mostofhumancancersaresolidtumors,onlyfewantibodiescanbeusedforsolidtumorstreatmentdu

etolowpenetratingabilityofconventionalantibody.Camelidimmunoglobulinsdifferfromth

eseantibodiesthatupto75%ofallserumproteinsareimmunoglobulinGmoleculeslackingligh

tchains,whichonlyconsistofheavychains.Theantigenbindingfragmentcontainsonlysingle

heavychainvariabledomain(VHH),whichcanbeeasilydisplayedbyphage

.TheVHHhasalowmolecularweightwhichimprovestheirbiodistributionandallowsabettertissuepenetration.

Thegenesencodingthesefragmentscaneasilybeengineeredtoobtainmulti-valentandmulti-specificformats

,orcanbere-clonedasfusiontoother(effectors)proteins,

whichpointouttheextraordinaryvalueofheavychainantibodiesasbiochemicalandpharmacologicaltools

.ThepenetratingVHHattacktumorsbymechanisms:1)opsonization,whichtriggerskillingbyimmunecells,

antly.Tofindoutbiomarkersofearlyeventofcardiovascularendotheliumishighlydesiredintreatmentanddiagnosisofatherosclerosisespeciallyinearlystage

.SelectionofVHHagainstunknownantigensexpressedatherosclerosisvesselscanbeperformedwi

thinjuredarteryderive

dfromapoE-/-mouse,whichisgenedefectanimalmodelthatdevelopsatherosclerosisbyfeedingfatdiet

.Forwellknowninhibitoryantibodyselection,highaffinityVHHcanobtainbyusingcommercialantigens

.AsVHHissolubleandwithhighlystableaffinityevenathighertemperature,

whichmakesthisantibodymoreapplicableinantigenlabelingandcouplingwithreagent

sthatmaymanipulateprogressofcardiovascularlesion.
Sinceintroductionofphagedisplaytechnologyinbiosynthetic,

VHHantibodyspecificforchosentargetscouldbeisolatedwithouttheneedforanimalimmunization.Becauseofsmallsize

,VHHcanbeproducedinbacterialcultureathighyields.

Biolabelingtechniquesfacilitateselectionofhighaffinityatlifecellsandanimalmodels

,whicheventuallyleadstoutilityofVHHinhumandiseases.

此行目的：
寻求有一定基础设施及药物研发力量生物制药企业，将已在西方国家广为研究的生物治疗药物推介并应用到生产流程中。



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