Chii chinonzi CAR-T (Chimeric Antigen Receptor T-cell)?
Kutanga, ngatitarisei nezvesimba remuviri wemunhu rekudzivirira zvirwere.
Sisitimu yekudzivirira muviri inoumbwa ne network yemasero, nyama, uye nhengo dzinoshanda pamwe chete kutichengetedza muviri. Rimwe remasero akakosha anobatanidzwa masero machena eropa, anonziwo maleukocyte,izvo zvinouya mumhando mbiri huru dzinosanganisa kutsvaga nekuparadza tupukanana tunokonzera zvirwere kanazvinhu.
Mhando mbiri huru dze leukocytes ndeidzi:
Ma phagocytes, masero anotsenga zvinhu zvinopinda mumuviri.
Lymphocytes, masero anobvumira muviri kuyeuka nekuziva zvakambopinda mumasero uye anobatsiramuviri unovaparadza.
Masero akasiyana-siyana anoonekwa sema phagocytes. Rudzi rwakajairika i neutrophil,iyo inonyanya kurwisa mabhakitiriya. Kana vanachiremba vachinetseka nezvehutachiona hwebhakitiriya, vanogona kurairakuongororwa ropa kuti uone kana murwere aine huwandu hwakawanda hwema neutrophils anokonzerwa nehutachiona.
Mamwe marudzi ephagocytes ane mabasa awo ekuona kuti muviri unopindura nemazvokune rudzi rwakati rwemupambi.
Mhando mbiri dzemalymphocytes iB lymphocytes neT lymphocytes. Lymphocytes dzinotangamumongo wemapfupa uye zvinogara imomo zvokura kuita masero eB, kana kuti zvinoenda ku thymusgland, kwadzinokura kuita masero eT. Malymphocyte eB nemalymphocyte eT ane zvikamu zvakasiyanamabasa: MaB lymphocytes akafanana nehurongwa hwehungwaru hwemauto emuviri, achitsvaga ruzivo rwavozvinangwa uye kutumira dziviriro kuti dzivavharire. Masero eT akafanana nemasoja, achiparadzavapambi vakaonekwa nehurongwa hwehungwaru.
Tekinoroji yemasero eT eChimeric antigen receptor (CAR): rudzi rwemasero ekugamuchiraimmunotherapy (ACI). Masero eT emurwere anogadzira CAR kuburikidza nekuvakazve majinitekinoroji, iyo inoita kuti masero eT anobatsira ave akanyanya kunangwa, anouraya uye anogara kwenguva refu kupfuuramasero emuviri enguva dzose, uye anogona kukunda nharaunda inodzvinyirira masoja emuviri yeKushivirira kwemuviri wemushonga wegomarara nekuputika. Uku kurapa kwakanangana nemasero emuviri wemushonga wegomarara.
Nheyo yeCART ndeyekubvisa "yakajairika" yemasero eT emuviri emurwere.uye enderera mberi nekugadzira majini, kuunganidza in vitro kune zvinangwa zvegomarara guruchombo chekurwisa vashandi "chimeric antigen receptor (CAR)", uye wobva waisa masero eT akachinjwakana murwere adzokera mumuviri wake, mareceptor matsva emasero akagadziriswa achafanana nekuisa radar system,iyo inokwanisa kutungamira masero eT kuwana nekuparadza masero ekenza.
Kubatsira kweCART paBPIH
Nekuda kwekusiyana kwemaumbirwo enzvimbo yechiratidzo chemukati memasero, CAR yakagadzira manazvizvarwa. Tinoshandisa CART yechizvarwa chitsva.
1stchizvarwa: Paiva nechikamu chimwe chete chechiratidzo chemukati memasero uye kudziviswa kwebundumhedzisiro yacho yakanga isina kunaka.
2ndchizvarwa: Yakawedzera molekyuru inokurudzira pamwe chete zvichibva pachizvarwa chekutanga, uyeKukwanisa kwemasero eT kuuraya bundu kwakavandudzika.
3rdchizvarwa: Zvichibva pachizvarwa chechipiri cheCAR, kugona kwemasero eT kudzivirira bundukuwanda kwemasero eropa uye kukurudzira apoptosis kwakavandudzika zvikuru.
4thKuzvarwa: Masero eCAR-T anogona kubatsira mukubvisa huwandu hwemasero egomarara kuburikidzakuita kuti transcription factor NFAT itange kushanda kuti interleukin-12 itange kushanda mushure meCARinoziva antigen inotarirwa.
| Chizvarwa | Kukurudzira Chinhu | Chinhu |
| 1st | CD3ζ | Kushanda kwemaseru eT chaiwo, seru reT rine chepfu, asi harina kukwanisa kuwanda nekurarama mumuviri. |
| 2nd | CD3ζ+CD28/4-1BB/OX40 | Wedzera costimulator, wedzera chepfu yemasero, kugona kushoma kwekuwedzera. |
| 3rd | CD3ζ+CD28/4-1BB/OX40+CD134 /CD137 | Wedzera ma costimulators maviri, vandudzakugona kuwanda uye chepfu. |
| 4th | Jini rekuzviuraya/CAR-T ine Amored (12IL) Enda kuCAR-T | Batanidza majini ekuzviuraya, simba rekudzivirira muviri rinoratidza simba remuviri, uye mamwe matanho chaiwo ekudzora. |
Maitiro ekurapa
1) Kupatsanurwa kwemasero machena eropa: Masero eT emurwere anopatsanurwa kubva muropa riri kunze kweropa.
2) Kushanda kwemasero eT: mabhora emagineti (masero e dendritic ekugadzira) akaputirwa nema antibodies ariinoshandiswa kumutsa masero eT.
3) Kuiswa kwemasero eT: Masero eT akagadziriswa majini kuti abudise CAR mu vitro.
4) Kuwedzera: Masero eT akagadziriswa majini anowedzerwa mumuviri wemunhu.
5) Kurapa nemakemikari: Murwere anorapwa nemakemikari asati aiswazve mumasero eT.
6) Kuwedzerwazve: Masero eT akagadziriswa majini anodzokera mumurwere.
Zviratidzo
Zviratidzo zveCAR-T
Nzira dzekufema: Kenza yemapapu (Small cell carcinoma, squamous cell carcinoma,adenocarcinoma), kenza yemudumbu, nezvimwewo.
Masisitimu ekugaya chikafu: kenza yechiropa, yemudumbu uye yemudumbu, nezvimwewo.
Sisitimu yeweti: Kidney neadrenal carcinoma uye metastatic cnacer, nezvimwewo.
Sisitimu yeropa: Acute uye chronic lymphoblastic leukemia (T lymphoma)zvisingabatanidzwi) nezvimwewo.
Dzimwe kenza: Melanoma inouraya, kenza yemazamu, kenza yeprostate nerurimi, nezvimwewo.
Kuvhiyiwa kubvisa gonda rekutanga, asi dziviriro yemuviri yakaderera, uye kurapwa kunononoka.
Mamota ane kupararira kwemasero eropa asingakwanise kuvhiyiwa.
Mhedzisiro yechemotherapy neradiotherapy yakakura kana kuti hainzwisisi chemotherapy neradiotherapy.
Dzivirira kuti bundu ridzokorore mushure mekuvhiyiwa, chemotherapy uye radiotherapy.
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 nekugadzira 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, zvichiwedzera huwandu hwemaantigen egomarara. Kurapa kweCAR T hakugumiriwo 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 wakakura wekubereka. Sezvo dzimwe nzvimbo dzichiratidzwa mumasero akawanda egomarara, akadai seEGFR, jini reCAR reantigen 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.