HydrogelsDeliverCAR-TcellsForSolid TumorTreatment
ThefullnameofCAR-TgenetherapyisChimericAntigenReceptor(CAR) T-cellTherapy.Chimericantigenreceptor(CAR)Tcelltherapyisaformof immunotherapyinwhichTcellsaretakenfromapatient'sbloodandplacedin alaboratorysettingtobemodifiedsothattheycanrecognizeanddestroy specificcancercellsThemodifiedTcellsarethendeliveredbacktothe patient.Oncebackinthepatient,themodifiedTcellscandetectcancercells anddestroythecancerbyharnessingthebody'sownimmuneresponseSince 2017,severalCAR-Ttherapiesapprovedformarketingarerelatedtothe treatmentofhematologicaltumors.Inthetreatmentofsolidtumors, CAR-Thasnotyetachievedsubstantialbreakthroughs.
3DhydrogelisastarcarrierinthefieldofdrugdeliveryThroughtunable materialandstructuredesign,itcannotonlymimicthenativeextracellular matrix(ECM)ofimmunetissuestomaintaincellviability,butalsodelivertothe defensesitesinthebodyinrealtimetoprolongtheresidencetimeofcarrying cells,thusimprovingtheeffectofimmunotherapyCouldhydrogelloaded CAT-TcellsbringCAR-Ttherapyonestepclosertosolidtumors?
1.NatureBiomedicalEngineering(IF=29.234):Localcontrolledrelease ofimmunecellsbasedon"cellwarehouse"forCAR-Ttherapyofsolid tumors;2021.4.26
CAR-Tcelltherapyhasencounteredmanysetbacksinthetreatmentofsolid tumors,largelyduetothephysiologicalbarrierofsolidtumorsandthe immunosuppressivenatureofthetumormicroenvironment,whichinhibitthe activityandsurvivalofCARTcellsUsingmethacrylylatedhyaluronicacid (HAMA)hydrogelasacarrier,theresearcherscombinedCARTcellstargeting CSPG4antigen(melanomaspecificantigen)andantiPDL1blocking antibodyboundhumanplatelets(PaPDL1)loadedintothehydrogelTo supporttheviabilityandproliferationofCARTcellsinthehydrogel,PLGA nanoparticlepackagedcytokineIL15wasalsoincorporatedThismethodcan beusedincombinationwithothertherapies(suchaschemotherapyand radiotherapy)tobetterinhibittumorrecurrenceandmetastasisAtthesame time,thenovelcelldeliverystrategyalsoprovidesnewideasforthetreatment ofothercelltherapiesandrelateddiseases
HuatengPharma https://ushuatengscicom Retinoblastoma(RB)isapediatricretinaltumorthatoverexpressesthe gangliosideGD2.Althoughearlydiagnosiscanbetreated,patientsmaylose oneortwoeyesTheresearchersselectedchitosanpolyethyleneglycol(PEG) thermosensitivehydrogelasthebestinjectablehydrogelforintraocular deliveryofCART(GD2specificchimericantigenreceptorTlymphocytes). MostoftheTcellsencapsulatedinthehydrogelremainedviableandwere releasedfromthegeltotheoutsidewithin1week.Theexperimentsfoundthat whencombinedwithlocallyreleasedinterleukin15andinjectedhydrogelGD2, CAR-TsuccessfullyeliminatedRBtumorcellswithoutcompromisingvisionin mice
HuatengPharma https://ushuatengscicom https://doiorg/101038/s4301802000119y
3.ACSAppliedMaterials&Interfaces(IF=10.383):Polypeptidehydrogels forCAR-Tproliferationandsolidtumorimmunotherapy;2022.8.9
InordertoobtainbetterclinicalefficacyofCARTtherapy,itisnecessaryto rapidlyexpandinashorttimetogeneratealargenumberoffunctionalTcells, andthecurrenttechnologycannotsolvethisproblemLongeroperatingtimes resultinthelossoralterationofthefunctionandphenotypeofCAR-Tcells, whichcanalsoleadtopatientslosingoptimaltreatmenttimeUsingFEFK(Fis phenylalanine,Eisglutamicacid,andKislysine)polypeptidehydrogelas carrier,theresearchersdesignedamicroenvironmentwithsimilarlymphoid organstoactivateandexpandimmunecells.Mimickingmatrixhydrogels showedoptimalstiffnessandadhesionliganddensity,whichacceleratedthe proliferationofCAR-Tcells.Meanwhile,theintrinsicPD-1blockingsingle chainvariablefragment(scFv)secretedbyengineeredCARTfurther enhancedcellproliferationandcytotoxicity.ComparedwithtraditionalCAR-T therapy,localizeddeliveryofCARTcellsfromscaffoldscanachievelongterm retention,significantlyinhibittumorgrowth,andincreaseinfiltrationofeffector TcellsWiththecontinuousindepthresearchofbioengineeringandgenetic engineeringmethods,CARTbasedcelltherapiesareexpectedtoachieve rapidexpansion,maintainandenhancefunctionalactivity,andsolvethe problemsofgreatclinicaldemandandtimeurgency
HuatengPharma https://ushuatengscicom
Originalarticle: CustomizedMultifunctionalPeptideHydrogelScaffoldsforCAR-T-Cell RapidProliferationandSolidTumorImmunotherapy https://doiorg/101021/acsami2c10727
4.Small(IF=15,153):InjectablehydrogelregulatoryTcellsforcancer immunotherapy;2022.6.17
Mitochondrialdysfunction-inducedTcellexhaustionisamajorobstacletoT cellbasedcancerimmunotherapyInaddition,thedeficiencyofmajor histocompatibilitycomplexI(MHCI)ontumorcellslimitstheefficiencyofTcell recognitionoftumorcellsandaffectstheirtherapeuticefficacyThesetwo factorsarethemainbarrierstocancerimmunotherapy.Basedonthis,the researchersusedoxidizedsodiumalginate(OSA)modifiedtumorcell membranevesicles(O-TMV)asagelator,andaxitinibisencapsulatedinthe lipidbilayerofOTMV,41BBantibodyandproproteinconvertase subtilisin/kexintype9inhibitorPF06446846nanoparticlesencapsulatedinthe cavitiesofhydrogelstodevelopaninjectablehydrogeltosimultaneously modulateTcellexhaustionandMHCIExpression,amplifiescancer immunotherapy
HuatengPharma https://ushuatengscicom
Originalarticle: AnInjectableHydrogeltoModulateTCellsforCancerImmunotherapy https://doiorg/101002/smll202202663
5.ScienceAdvances(IF=14.957):"Coating"CAR-Tcellsontumorsto enhanceefficacy;2022.4.2
Forbloodcancerssuchasleukemiaandlymphoma,approvedCART therapieshavebenefitedmanypatients.However,forsolidtumors,theroleof CARTtherapyhasbeenlimitedBraintumors,livertumors,stomachcancers, etc.,aregenerallysolidtumorsthatarelocatedinspecificlocationsandform densetumorsthatarenoteasilyrecognizedbyimmunecellsAnditisdifficult forCAR-Tcellstopenetrateandattackcancercells.Theresearchersused hydroxypropylmethylcelluloseandPEGbPLAcopolymerasaninjectable hydrogelcarriertotemporarily"package"CAR-Tcellsandstimulatory cytokinestogetherUsingasyringe,thegelis"applied"nearthetumor,where Tcellscangrowandproliferate,andarecontinuouslyreleasedfromthegelto encirclethecancercells
Originalarticle: DeliveryofCAR-Tcellsinatransientinjectablestimulatoryhydrogel nicheimprovestreatmentofsolidtumors https://wwwscienceorg/doi/101126/sciadvabn8264
6.JournaloftheAmericanChemicalSociety(IF=7.571):Tlymphocyte captureDNAnetworkforlocalimmunotherapy;2021.11.15
Efficientisolationofimmunecellswithhighpurityandlowcellulardamageis animportantpartofimmunotherapy,butitremainsahighchallengeThe
https://ushuatengscicom researchersdesignedacelltrappingDNAnetworkhydrogelcontaininga multivalentmultiphantomforthespecificisolationandinsitucultureofT lymphocytes(Tcells)TwoultralongDNAchainssynthesizedbyanenzymatic amplificationprocesswererationallydesignedtoincludefunctional multimodulesascellularanchorsandimmuneadjuvants.Complementary sequencesfacilitateDNAnetworkformationandTcellencapsulation,and providerestrictionendonucleasecleavagesitesforreactivereleaseofTcells andimmuneadjuvantsThepurityofthecapturedtumorinfiltratingTcellswas 98%,andthesurvivalratewasabout90%.Tcell-containingDNAnetworksare furtherusedforlocalimmunotherapyoftumorlesionsTheresearchwork providesapowerfulnanobiotechnologyfortheefficientisolationofimmune cellsandotherbiologicalparticles
https://ushuatengscicom TheroleofCARTcellsinthetreatmentofsolidtumorsislimitedduetopoor transportofCARTcellsinjectedintothetumorsiteandthelimitedinfiltration andsurvivalofthecellsintheimmunosuppressedandhypoxictumor microenvironment(TME)Thisstudyproposesasodiumalginategelbased injectableimmunemicrochip(iG/MC)systemthatdeliversCARTcellswithin tumorsandimprovestheirtherapeuticefficacyinsolidtumorsTheresults showedthatoxygencarrierandIL-15synergisticallyenhancedthesurvival andexpansionofCARTcellsunderhypoxia,andimprovedtheefficacyof CAR-Tcells.
HuatengPharma https://ushuatengscicom 9.Biomaterials(IF=15.304):3DhydrogelsthatpromoteTcell proliferation;2020.8.13
TherearestillmanylimitationsofTcellsinthefieldofimmunotherapy,suchas thedifficultyofproducinglargequantitiesoftherapeuticTcellsinashort periodoftimeinaneconomicalandfeasiblemannerTheresearchers designedathree-dimensional(3D)polyethyleneglycol(PEG)hydrogel covalentlyboundtolowmolecularweightheparin,designedtoresemblea lymphnodewhereTcellsmultiply.Amongthem,PEGprovidedthedesired structuralandmechanicalproperties,whileheparinwasusedtoanchorthe cytokineCCL21(CCL21ispresentinlymphnodesandcanaffectcell migrationandproliferation)Comparedwithstateoftheartexpansionsystems consistingofartificialantigen-presentingcells,3Dhydrogelshavesuperior loadingcapacityandtheabilitytopromoteCD4+Tcellproliferation
Originalarticle: CCL21-loaded3DhydrogelsforTcellexpansionanddifferentiation https://doi.org/10.1016/j.biomaterials.2020.120313
10.AdvHealthcareMaterials(IF=11.092):Automaticexpansionof primaryhumanTcellsinhydrogelmicrotubulesforimmunotherapy; 2018.5.11
Immunotherapyisahighlyeffectivestrategyforthetreatmentofmanyhuman cancers,andiscommonlyusedinmelanoma,cervicalcancer,lymphoma,and leukemiaThestudyculturedTcellssuspendedinmicroscalealginate
https://ushuatengscicom hydrogeltubes(AlgTubes),whichprotectcellsfromhydrodynamicstressand limitcellmassto400µm(radialdiameter)toensureefficientmasstransport andcreateacellfriendlymicroenvironmentforTcellgrowthUnderoptimized cultureconditions,TcellsculturedbyAlgTubeshavehighcellviability,low DNAdamage,highgrowthrate(320foldexpansionin14days),highpurity (≈98%CD3+)andhighyield(32×108cells/ml)Thismethodhasgreater applicationadvantagesthanthecurrentTcellculturemethodintermsof cultureamount,time,costandyield
HuatengPharma https://ushuatengscicom CARTgenetherapyisanewtypeofprecisiontargetedtherapyforcancer treatment.Itisaverypromisingnewtumorimmunotherapymethodthatcanbe precise,rapid,efficient,andhasthepotentialtocurecancerCARTtherapy involvesaseriesofstepssuchasisolation,modification,amplificationand reinfusion.Asafunctionalcarrier,hydrogelplaysanimportantroleinthetwo stepsofamplificationandreinfusion
Inrecentyears,theapplicationofhydrogelsinbiomaterials,tissueengineering, drugreleaseandotherfieldshasbecomeahotspotofscientificresearch. Amongthem,polyethyleneglycol(PEG)hydrogelhasthecharacteristicsof goodbiocompatibility,non-toxicityandlowimmunogenicity,andhasagood applicationprospectHuateng
Pharmaprovides4-ArmPEG-SS,4-ArmPEG-SG,8-ArmPEG-SSand8-ArmP EGSGwithMW2k,5K,10K,or20K,whichcanbeusedashydrogelsfor medicaldevices.AndwecanalsoprovidePEGderivativesfor3Dbioprinting.
Relatedarticle: GlobalCARTcellTherapyDevelopmentProgress