简介：Thecurrentconceptof“AdoptiveTCellImmunotherapyofCancer”isquitedifferentfromhowitwasoriginallyconceived．Withthedevelopmentofmoderntechnologyinmolecularbiology,cellbiology，immunologyandbiochemistryduringthelasttwentyyearsorso，adoptiveimmunotherapyhasgrownfromitsinitialformofasimple“bloodcelltransfer”intoitspresentprocesswhichinvolveshostvauccination，effectorcellactivation／polarizationandgeneticmodification．Withtheuseofimmuneadjuvantsandtheidentification／characterizationoftumor-reactiveTcellsubsets，orincombinationwithothertherapeuticstrategies，adoptivelytransferredTcellshavebecomemuchmorepotentinmediatingtumorregression．Inaddition，studiesonthetraffickingofinfusedTcells，celltransferperformedinlymphopenicmodels，aswellasthediscoveryofnoveltechniquesinimmunemonitoringforthegenerationofeffectorcellsinvitroandaftercelltransferinvivohaveprovidedusefultoolstofurtherimprovethetherapeuticefficacyofthisapproach．ThisarticlewillreviewtheserelatedaspectsofadoptiveTcellimmunotherapyofcancerwithspecificcommentsoncertaincriticalareasintheapplicationofthisapproach．Withtherapidlyevolvingadvancesinthisarea，itishopedthatthiscellularimmunologictherapyasitwasconceptualizedinthepast，canbecomemoreusefulinthetreatmentofhumancancerinthenearfuture．

简介：InordertoimprovethefunctionalaffinityofthehumanizedVHsingledomainantibodyagainsthumanlungcancer,thegenescodingthehomogenousdimersdihu3D3V_Handtetramerstehu3D3V_HwereconstructedbyfusingtheSVS-Cysshortpeptideandp53tetramerizationstructuraldomaingenetohu3D3V_HgeneviarecombinantPCRtechnique,respectively.Then,thedihu3D3V_Handtehu3D3V_HgeneswereclonedtotheprokaryoticexpressionvectorpET-22b(+)andexpressedinE.coliBL21(DE3).TheproteinsexpressedwerepurifiedthroughNi~(2+)-affinitychromatographiccolumn.Meanwhile,thehu3D3V_H,dihu3D3V_Handtehu3D3V_HproteinswerelabeledwithFITC,andtheirreactivitywithan-tigenandspecificitywereanalyzedbyimmunofluorescenceassay.Astotheirfunctionalaffinities,itwasanalyzedandcomparedbyflowcytometry.Theresultsindicatedthatthesetwogeneswereexpressedasmonomersandmainlyasinclusionbodies.Afterpurificationandrenaturation,therewereabout50%ofdimersand70%oftetramerremainingintheproteinsolution.Inaddition,thedihu3D3V_Handte-hu3D3V_Hproteinsstillremainedthereactivitywithantigenandspecificityofhu3D3V_Hprotein,andtheirfunctionalaffinitieswereincreasedabout60%or100%respectively,comparedwiththoseofhu3D3V_Hprotein.Itisevidentthatthefunctionalaffinityofhu3D3V_Hproteincanbegreatlyimprovedbyincreasingitsbindingvalency.

简介：Toinvestigatethemutationsintheupstreamregulatoryregion(URR)ofhumanpapillomavirustype16(HPV-16)fromthecervicalcancerbiopsiesinXinjiangUygurwomenanditsrelationshiptothehighincidenceofcervicalcancerinthesouthernXinjiang,thetissueDNAwasextractedfromthecervicalcancerbiopsies,andtheURRsegmentofHPV-16DNAwasamplified,sequencedandanalyzed.Thereafter,thepolymorphismofURRinHPV-16wasthenanalyzed.ItwasdemonstratedthatthepositiveratedetectedforthepresenceofURRinHPV-16was89.47%(17/19).ComparedwiththepreviouslypublishedsequenceinURRofprototypeHPV-16,somemutationsweredetectedinthesequenceofURR.Themutationsin17URRfragmentsofHPV-16couldbedividedinto11patterns(XJU-1toXJU-11)atnucleicacidlevel,inwhicheachofXJU-1andXJU-4accountedfor23.53%(4/17),andotherpatternsofmutationaccountedfor5.88%(1/17).IncomparisonwiththeURRofprototypeHPV-16,theDNAidentityofthesepatternswas98.50%-99.68%.Inthese17URRfragments,twopointmutationsoccurredatposition7192(GtoT)andposition7520(GtoA)andtheyappearedtobeconstantinXinjiangarea.ThesetwomutationswereubiquitousintheAsia-Americantypeandconferredstronginfectionactivityandcarcinogenicityofthisvirus.Inaddition,themutationsatposition7729(AtoC),position7843(AtoG)andposition7792(CtoT)couldenhanceitstranscriptionactivityconsiderably.ItisconcludedthatsomemutationsoccurinURRgeneofHPV-16inthecervicalcancerbiopsiestakenfromUygurwomeninXinjiangarea,suggestingthatcertainrelationshipexistsamongthemutationsinURRofHPV-16,thephylogenyofHPV-16andthehighincidenceofcervicalcancerinsouthernpartofXinjiangarea.

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