Chii chinonzi CAR-T (Chimeric Antigen Receptor T-cell)?
Kutanga, ngatitarisei nezvesimba remuviri wemunhu rekudzivirira zvirwere.
Masisitimu ekudzivirira muviri anoumbwa neboka remasero, nyama, uye nhengo dzinoshanda pamwe chete kudzivirira muviri. Rimwe remasero akakosha anobatanidzwa masero machena eropa, anonziwo maleukocyte, anouya mumhando mbiri huru dzinosangana kuti dzitsvage uye dziparadze tupukanana tunokonzera zvirwere.
Mhando mbiri huru dze leukocytes ndeidzi:
Ø phagocytes, masero anotsenga zvipembenene zvinopinda
Ø lymphocytes, masero anobvumira muviri kuyeuka nekuziva zvakambopinda mumuviri uye kubatsira muviri kuzviparadza
Masero akasiyana-siyana anoonekwa semaphagocytes. Rudzi rwakajairika i neutrophil, iyo inonyanya kurwisa mabhakitiriya. Kana vanachiremba vachinetseka nezvehutachiona hwebhakitiriya, vanogona kuraira kuongororwa kweropa kuti vaone kana murwere aine huwandu hwakawanda hwema neutrophils anokonzerwa nehutachiona. Mamwe marudzi emaphagocytes ane mabasa awo ekuona kuti muviri unopindura zvakakodzera kune rudzi rwakati rwechirwere.
Marudzi maviri emalymphocytes ndiwo maB lymphocytes neT lymphocytes. MaLymphocytes anotangira mumongo wemapfupa uye anoramba aripo obva akura kuita masero eB, kana kuti anobuda achienda kuthymus gland, kwaanokura kuita masero eT. MaB lymphocytes neT lymphocytes ane mabasa akasiyana: MaB lymphocytes akafanana nehurongwa hwehungwaru hwemauto emuviri, achitsvaga zvinangwa zvawo uye anotumira dziviriro kuti dzivavharire. MaT cell akafanana nemasoja, achiparadza vapambi vakaonekwa nehurongwa hwehungwaru.
Masisitimu ekudzivirira muviri anoumbwa neboka remasero, nyama, uye nhengo dzinoshanda pamwe chete kudzivirira muviri. Rimwe remasero akakosha anobatanidzwa masero machena eropa, anonziwo maleukocyte, anouya mumhando mbiri huru dzinosangana kuti dzitsvage uye dziparadze tupukanana tunokonzera zvirwere.
Mhando mbiri huru dze leukocytes ndeidzi:
Ø phagocytes, masero anotsenga zvipembenene zvinopinda
Ø lymphocytes, masero anobvumira muviri kuyeuka nekuziva zvakambopinda mumuviri uye kubatsira muviri kuzviparadza
Masero akasiyana-siyana anoonekwa semaphagocytes. Rudzi rwakajairika i neutrophil, iyo inonyanya kurwisa mabhakitiriya. Kana vanachiremba vachinetseka nezvehutachiona hwebhakitiriya, vanogona kuraira kuongororwa kweropa kuti vaone kana murwere aine huwandu hwakawanda hwema neutrophils anokonzerwa nehutachiona. Mamwe marudzi emaphagocytes ane mabasa awo ekuona kuti muviri unopindura zvakakodzera kune rudzi rwakati rwechirwere.
Marudzi maviri emalymphocytes ndiwo maB lymphocytes neT lymphocytes. MaLymphocytes anotangira mumongo wemapfupa uye anoramba aripo obva akura kuita masero eB, kana kuti anobuda achienda kuthymus gland, kwaanokura kuita masero eT. MaB lymphocytes neT lymphocytes ane mabasa akasiyana: MaB lymphocytes akafanana nehurongwa hwehungwaru hwemauto emuviri, achitsvaga zvinangwa zvawo uye anotumira dziviriro kuti dzivavharire. MaT cell akafanana nemasoja, achiparadza vapambi vakaonekwa nehurongwa hwehungwaru.
Tekinoroji yeT cell yeChimeric antigen receptor (CAR): imhando yekurapa masero ekudzivirira chirwere (ACI). T cell yemurwere inogadzira CAR kuburikidza netekinoroji yekuvakazve majini, iyo inoita kuti T cells dzinoshanda dzive dzakanangwa zvakanyanya, dzinouraya uye dzinogara kwenguva refu kupfuura masero ekudzivirira chirwere akajairwa, uye dzinogona kukunda mamiriro ekunze ekudzivirira chirwere chegomarara uye kuputsa kushivirira kwemuviri. Iyi imishonga chaiyo yekudzivirira gomarara kubva kumasero ekudzivirira chirwere.
Nheyo yeCART ndeyekubvisa "yakajairika" yemasero eT emuviri emurwere uye kuenderera mberi nekugadzira majini, kuunganidza in vitro kuti uwane zvinangwa zvegomarara re "chimeric antigen receptor (CAR)" rezvombo zvikuru zvekurwisa vashandi, uye wozodzosera masero eT akachinjwa mumuviri wemurwere, mareceptor matsva emasero akachinjwa achafanana nekuisa radar system, iyo inokwanisa kutungamira masero eT kuwana nekuparadza masero ekenza.
Kubatsira kweCART paBPIH
Nekuda kwekusiyana kwemaumbirwo enzvimbo yesignali yemukati memasero, CAR yakagadzira zvizvarwa zvina. Isu tinoshandisa CART yechizvarwa chazvino.
1stKuzvarwa: Kwaingova nechikamu chimwe chete chechiratidzo chemukati memasero uye mhedzisiro yekudzivisa bundu yakanga isina kunaka.
2ndKuberekwa: Kwakawedzerwa molekyuru inosimudzira muviri zvichibva pachizvarwa chekutanga, uye kugona kwemasero eT kuuraya bundu kwakavandudzika.
3rdKuzvarwa: Zvichibva pachizvarwa chechipiri cheCAR, kugona kwemasero eT kudzivirira kuwanda kwegomarara uye kukurudzira apoptosis kwakavandudzika zvakanyanya.
4thKugadzirwa: Masero eCAR-T anogona kubatanidzwa mukubviswa kwemasero egomarara nekushandisa NFAT iyo iri pasi pemuchina we transcription kuti iite interleukin-12 mushure mekunge CAR yaona antigen iri kutarisirwa.
Maitiro ekurapa
1) Kuparadzaniswa kwemasero machena eropa: Masero eT emurwere anoparadzaniswa neropa rekunze;
2) Kushanda kwemasero eT: mabhora emagineti (masero edendritic ekugadzira) akaputirwa nema antibodies anoshandiswa kushanda kwemasero eT;
Kuiswa kwemasero eT: Masero eT akagadziriswa majini kuti abudise CAR mumuviri wemunhu.
3) Kuwedzera: Masero eT akagadziriswa majini anowedzerwa mumuviri wemunhu.
4) Kurapa nemakemikari: Murwere anorapwa nemakemikari asati aiswazve mumasero eT;
5) Kuwedzerwazve: Masero eT akagadziriswa majini anodzokera mumurwere.
Zvakanakira:
1)Masero eCAR T anonyanya kurwiswa uye anogona kuuraya masero egomarara ane antigen chaiyo zvinobudirira.
2)Kurapa nemasero eCAR-T kunoda nguva shoma. CAR T inoda nguva pfupi yekukura masero eT nekuti inoda masero mashoma pasi pemhedzisiro imwe chete yekurapa. Kukura kwemasero emuviri kuburikidza ne vitro kunogona kupfupikiswa kusvika kumavhiki maviri, izvo zvakaderedza nguva yekumirira zvakanyanya.
3)CAR inogona kuziva kwete maantigen epeptide chete, asiwo maantigen eshuga nemafuta, zvichiita kuti maantigen egomarara awedzere. Kurapa kweCAR T hakugumiriswiwo nemaantigen eprotein emasero egomarara. CAR T inogona kushandisa maantigen eshuga nemafuta asiri mapuroteni emasero egomarara kuona maantigen muzvikamu zvakasiyana-siyana.
4)CAR-T ine mukana wekuwedzera huwandu hwemasero ekenza. Sezvo mamwe ma places achiratidzwa mumasero akawanda egomarara, akadai seEGFR, gene reCAR re antigen iyi rinogona kushandiswa zvakanyanya kana ragadzirwa.
5)Masero eCAR T ane basa rekuchengetedza immune memory uye anogona kurarama mumuviri kwenguva yakareba. Zvakakosha zvikuru kudzivirira kudzoka kwegomarara.