Chii chinonzi CAR-T (Chimeric Antigen Receptor T-cell)?
Kutanga, ngatitarisei gadziriro yomuviri yokuzvidzivirira kwomunhu.
Iwo immune system inoumbwa netiweki yemasero, matishu, uye nhengo dzinoshanda pamwe chete kuchengetedza muviri.Rimwe remaseru akakosha anosanganisirwa masero machena eropa, anonziwo leukocytes, anouya mumhando mbiri dzekutanga dzinosangana kutsvaga nekuparadza zvipenyu kana zvinhu zvinokonzeresa zvirwere.
Mhando mbiri dzekutanga dze leukocyte ndeidzi:
Ø phagocytes, masero anotsenga zvipenyu zvinopinda
Ø lymphocytes, masero anobvumira muviri kuyeuka uye kuziva vapambi vekare uye kubatsira muviri kuvaparadza
Nhamba yemasero akasiyana-siyana anonzi phagocytes.Rudzi runonyanya kuzivikanwa ndeye neutrophil, iyo inonyanya kurwisa mabhakitiriya.Kana vanachiremba vachinetseka nezvehutachiona hwehutachiona, vanogona kuraira kuongororwa ropa kuti vaone kana murwere aine nhamba yakawedzera yeutrophils inokonzerwa nehutachiona.Mamwe marudzi emaphagocytes ane mabasa awo ega kuti ave nechokwadi chokuti muviri unopindura zvakakodzera kune imwe mhando yevapambi.
Mhando mbiri dze lymphocytes dzinoti B lymphocytes uye T lymphocytes.Lymphocyte inotanga mumwongo webhonzo uye inogona kugara ipapo uye inokura kuva B masero, kana kuti inoenda ku thymus gland, kwainokura kuva T masero.B lymphocytes uye T lymphocytes ane mabasa akasiyana: B lymphocytes akafanana neuto remuviri wehungwaru, kutsvaga zvavanoda uye kutumira zvidziviriro kuti zvivhare pazviri.T masero akafanana nemasoja, achiparadza vapambi avo vanozivikanwa nesangano reungwaru.
Iwo immune system inoumbwa netiweki yemasero, matishu, uye nhengo dzinoshanda pamwe chete kuchengetedza muviri.Rimwe remaseru akakosha anosanganisirwa masero machena eropa, anonziwo leukocytes, anouya mumhando mbiri dzekutanga dzinosangana kutsvaga nekuparadza zvipenyu kana zvinhu zvinokonzeresa zvirwere.
Mhando mbiri dzekutanga dze leukocyte ndeidzi:
Ø phagocytes, masero anotsenga zvipenyu zvinopinda
Ø lymphocytes, masero anobvumira muviri kuyeuka uye kuziva vapambi vekare uye kubatsira muviri kuvaparadza
Nhamba yemasero akasiyana-siyana anonzi phagocytes.Rudzi runonyanya kuzivikanwa ndeye neutrophil, iyo inonyanya kurwisa mabhakitiriya.Kana vanachiremba vachinetseka nezvehutachiona hwehutachiona, vanogona kuraira kuongororwa ropa kuti vaone kana murwere aine nhamba yakawedzera yeutrophils inokonzerwa nehutachiona.Mamwe marudzi emaphagocytes ane mabasa awo ega kuti ave nechokwadi chokuti muviri unopindura zvakakodzera kune imwe mhando yevapambi.
Mhando mbiri dze lymphocytes dzinoti B lymphocytes uye T lymphocytes.Lymphocyte inotanga mumwongo webhonzo uye inogona kugara ipapo uye inokura kuva B masero, kana kuti inoenda ku thymus gland, kwainokura kuva T masero.B lymphocytes uye T lymphocytes ane mabasa akasiyana: B lymphocytes akafanana neuto remuviri wehungwaru, kutsvaga zvavanoda uye kutumira zvidziviriro kuti zvivhare pazviri.T masero akafanana nemasoja, achiparadza vapambi avo vanozivikanwa nesangano reungwaru.
Chimeric antigen receptor (CAR) T cell tekinoroji: imhando yekugamuchira cellular immunotherapy (ACI).T sero remurwere rinoratidza CAR kuburikidza neiyo genetic reconstruction tekinoroji, iyo inoita kuti masero eT aite akanyanya kunangwa, anouraya uye anoshingirira kupfuura akajairwa maseru edziviriro, uye anogona kukunda emuno immunosuppressive microenvironment yebundu uye kuputsa host immune kushivirira.Iyi ndiyo chaiyo immune cell anti - tumor therapy.
Nheyo yeCART ndeyekutora "yakajairika vhezheni" yemurwere ega immune T masero uye kuenderera mberi neinjiniya yemajini, kuunganidza mu vitro kune bundu rakanangana nechombo chikuru chinorwisa vanhu "chimeric antigen receptor (CAR)", wobva waisa shanduko. Masero eT adzokera mumuviri wemurwere, nyowani yakagadziridzwa sero receptors ichaita sekuisa radar system, iyo inokwanisa kutungamira masero eT kutsvaga nekuparadza maseru ekenza.
Zvakanakira CART paBPIH
Nekuda kwekusiyana kwechimiro cheiyo intracellular signal domain, CAR yakagadzira zvizvarwa zvina.Isu tinoshandisa yazvino chizvarwa CART.
1stchizvarwa: Paingova nechikamu chimwe chete chechiratidzo che intracellular uye tumor inhibition effect yakanga isina kunaka.
2ndchizvarwa: Yakawedzera co-inokurudzira molecule pahwaro hwechizvarwa chekutanga, uye kugona kweT masero kuuraya mapundu kwakavandudzwa.
3rdchizvarwa: Kubva pachizvarwa chechipiri cheCAR, kukwanisa kweT masero ekudzivisa kupararira kwechirwere uye kukurudzira apoptosis kwakavandudzwa zvakanyanya.
4thchizvarwa: Maseru eCAR-T anogona kubatanidzwa mukubvisirwa kwebundu cell population nekumisikidza yakadzika pasi transcription factor NFAT kuti iite interleukin-12 mushure mekunge CAR yaziva chinangwa cheantigen.
Kurapa nzira
1) Kuparadzaniswa kwesero jena reropa: Masero eT evarwere akaparadzaniswa neropa reparutivi;
2) T cell activation: magnetic beads (artificial dendritic cells) akaputirwa ne antibodies anoshandiswa kuita masero eT;
Transfection: T masero anogadzirwa genetically engineered kuratidza CAR in vitro.
3) Amplification: Iwo maT masero akagadziridzwa anokwidziridzwa mu vitro.
4) Chemotherapy: Murwere anotanga kurapwa nekemotherapy pamberi peT cell reinfusion;
5) Re-infusion: Genetically modified T masero anopinza zvakare mumurwere.
Zvakanakira:
1)Masero eCAR T anonangidzirwa zvakanyanya uye anogona kuuraya bundu maseru ane antigen chaiyo zvakanyanya.
2)CAR-T cell therapy inoda nguva shoma.CAR T inoda nguva shoma shoma kune tsika T masero nokuti inoda masero mashoma pasi pemaitiro akafanana ekurapa.Iyo vitro tsika kutenderera inogona kupfupikiswa kusvika kumavhiki maviri, izvo zvakanyanya kuderedza nguva yekumirira.
3)CAR haigone kuziva kwete peptide antigens chete, asiwo shuga uye lipid antigens, ichiwedzera tarisiro yemhando ye tumor antigens.CAR T kurapa zvakare haina kuganhurirwa neprotein antigens e tumor cell.CAR T inogona kushandisa shuga uye lipid asiri-protein maantigen emamota maseru kuona maantigen muzvikamu zvakawanda.
4)CAR-T ine imwe yakafara - spectrum reproducibility.Sezvo mamwe masayiti achiratidzwa mune akawanda bundu maseru, akadai seEGFR, CAR gene yeiyi antigen inogona kushandiswa zvakanyanya kana ichinge yavakwa.
5)Masero eCAR T ane immune memory function uye anogona kurarama ari mumuviri kwenguva yakareba.Izvo zvakakosha zvekiriniki kudzivirira bundu kudzoka.