Antibodiesareidealdrugcandidatesduetotheirhighspecificityfortarget molecules.Monoclonalantibodiesrepresentoneofthefastestgrowingsegmentsof thedrugmarket,however,recentattentionhasfocusedonpolyclonalantibodies andmonoclonalmixturestoreducetheopportunityforadiseasetobecomedrug resistant.Polyclonalantibodiessampledfromdiseasesurvivorsorimmunized hostsofferawealthofnewdrugcandidates.Currentpipelinesforinvestigatingthe immuneresponserelyonhybridomatechnology,whichistime-?consuminganddoes notcomeclosetomimickingthediversityofantibodiespresentintheorganism. NextgenerationsequencingofB-?cellscandeeplyinterrogatetheimmuneresponse, however,thistechnologyfallsshortofprovidinginsightintothebestantibodydrug candidates. WeproposethedevelopmentofValens-?Poly,whichwillintegratemass spectrometry-?basedproteomicsdatawithnextgenerationsequencingofB-?cells,an emergingfieldcalledimmunoproteogenomics.Byinterrogatingtheimmune responseattheprotein-?level,Valens-?Polywillbeabletorankantibodysequences basedontheirabundance,whichisaproxyforspecificitytotheantigenofinterest. ItisimpossibletosequenceallmemoryB-?cellsinahostorganism,thereforethe antibodysequencesreportedwouldonlyrepresentasmallfractionoftheantibodies thatcouldbepresent.Usingourpatentedspectralnetworkapproach,pioneeredin ourmonoclonalantibodysequencingtool,Valens,wewillbeabletorecover complementarity-?definingregions(CDRs)ofantibodiesevenwhentheB-?cellwas notcapturedfornextgenerationsequencing. Finally,wewillcharacterizethebroadspectrumofantibodiesproducedas partoftheimmuneresponse,calledtheantibodyrepertoire.Identifyingchangesin germlinegeneusageandtrackingcloneabundanceandlineageinresponseto immunizationoracrosspatientsisanimportantcomponentofcharacterizing diseasesandguidingdrugdiscovery.
Characterizationoftheantibodyresponsetoaninfectionisanimportantprecursor toantibody-?baseddrugdevelopment.Hereweproposeatool,Valens-?Poly,which identifyabundantantibodyspeciesbyintegratingmassspectrometryand nucleotidesequencingofmatureB-?cells.Ourtechnologywillcircumventtheneed forhybridomadevelopmentsavingoveramonthofdevelopmenttime,andwill consequentlyenablenoveldrugdiscoveriesandshortendrugdevelopment timelines.