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 pamwechete kutichengetedza muviri.Rimwe remasero akakosha anobatanidzwa masero machena eropa, anonziwo leukocytes,izvo zvinouya mumhando mbiri dzakakosha dzinosangana kutsvaga nekuparadza zvipenyu zvinokonzeresa zvirwere kanazvinhu.
Mhando mbiri dzekutanga dze leukocyte ndeidzi:
Phagocytes, masero anotsenga zvipenyu zvinopinda.
Lymphocytes, masero anobvumira muviri kuyeuka uye kuziva vapambi vekare uye rubatsiromuviri uvaparadze.
Nhamba yemasero akasiyana-siyana anonzi phagocytes.Rudzi runonyanya kuzivikanwa ndeye neutrophil,iyo inonyanya kurwisa mabhakitiriya.Kana vanachiremba vachinetseka nezvehutachiona hwehutachiona, vanogona kurairakuongororwa ropa kuona kana murwere ane nhamba yakawedzera yeutrophils inokonzerwa nehutachiona.
Mamwe marudzi emaphagocytes ane mabasa awo ega kuti ave nechokwadi chokuti muviri unopindura zvakakodzerakune imwe mhando yevapambi.
Mhando mbiri dze lymphocytes dzinoti B lymphocytes uye T lymphocytes.Lymphocytes inotangamumwongo webhonzo uye kana kugara ipapo uye kukura kuva B masero, kana ivo vanoenda kune thymusgland, kwavanokura kuva T masero.B lymphocytes uye T lymphocytes dzine zvakasiyanamabasa: B lymphocytes akafanana nemuviri wemauto ehungwaru, achitsvaga yavozvinangwa uye kutumira zvidziviriro kuvhara pazviri.T masero akafanana nemasoja, achiparadzavapambi vakaonekwa neve Intelligence.
Chimeric antigen receptor (CAR) T cell tekinoroji: imhando yekugamuchira maseruraimmunotherapy (ACI).T sero remurwere rinoratidza CAR kuburikidza nekugadzirisa genetictekinoroji, iyo inoita kuti masero eT anoshanda atariswe zvakanyanya, anouraya uye anopfuurira kupfuuramasero edziviriro edziviriro, uye anogona kukunda yemuno immunosuppressive microenvironment yebundu uye break host immune tolerance.Iyi ndiyo chaiyo immune cell anti - tumor therapy.
Nheyo yeCART ndeyekutora "yakajairika vhezheni" yemurwere pachake immune T maserouye enderera mberi nejini engineering, unganidza mu vitro kune bundu rakanangana nehukuruantipersonnel weapon "chimeric antigen receptor (CAR)", wobva wapinza masero eT akachinja.kudzoka mumuviri wemurwere, nyowani yakagadziridzwa cell receptors ichaita sekuisa radar system,iyo inokwanisa kutungamira masero eT kuwana uye kuparadza masero ekenza.
Zvakanakira CART paBPIH
Nekuda kwekusiyana kwechimiro cheiyo intracellular signal domain, CAR yakagadzira inazvizvarwa.Isu tinoshandisa yazvino chizvarwa CART.
1stchizvarwa: Paingova nechikamu chimwe chete chechiratidzo chemukati uye iyo tumor inhibitionmhedzisiro yaive yakaipa.
2ndchizvarwa: Yakawedzera co-inokurudzira molecule pahwaro hwechizvarwa chekutanga, uye iyokukwanisa kweT masero kuuraya mapundu kwakavandudzwa.
3rdchizvarwa: Kubva pachizvarwa chechipiri cheCAR, kukwanisa kweT masero kuvharidzira bundukuwanda uye kukurudzira apoptosis kwakagadziridzwa zvakanyanya.
4thchizvarwa: Maseru eCAR-T anogona kubatanidzwa mukubvisirwa kwebundu cell huwandu nekushandura iyo yakadzika yerunyoro chinhu NFAT kupinza interleukin-12 mushure meCARinoziva inotarirwa antigen.
| Generation | Kukurudzira Factor | Feature |
| 1st | CD3ζ | Yakananga T cell activation, cytotoxic T cell, asi haina kukwanisa kuwedzera uye kurarama mukati memuviri. |
| 2nd | CD3ζ+CD28/4-1BB/OX40 | Wedzera costimulator, kunatsiridza sero toxicity, kushoma kuwanda kugona. |
| 3rd | CD3ζ+CD28/4-1BB/OX40+CD134 /CD137 | Wedzera 2 macostimulators, gadzirisakuwanda kugona uye chepfu. |
| 4th | Kuzviuraya gene/Amored CAR-T (12IL) Enda CAR-T | Batanidza jini rekuzviuraya, ratidza immune factor uye mamwe matanho chaiwo ekudzora. |
Kurapa nzira
1) Kuparadzaniswa kwesero jena reropa: T masero emurwere akaparadzaniswa kubva kuropa remukati.
2) T masero activation: magineti bead (yekugadzirwa dendritic masero) akaputirwa nemasoja ekudzivirira chirwere ari.anoshandiswa kushandura T masero.
3) Transfection: T masero anogadzirwa genetically engineered kuratidza CAR in vitro.
4) Amplification: Iwo maT masero akagadziridzwa anokwidziridzwa mu vitro.
5) Chemotherapy: Murwere anotanga kurapwa nekemotherapy pamberi peT cell reinfusion.
6) Re-infusion: Genetically modified T masero anopinza zvakare mumurwere.
Zviratidzo
Zviratidzo zveCAR-T
Sistimu yekufema: Kenza yemapapu (Small cell carcinoma, squamous cell carcinoma,adenocarcinoma), kenza yenasopharynx, nezvimwewo.
Digestive system: Chiropa, dumbu uye colorectal cancer, nezvimwe.
Urinary system: itsvo uye adrenal carcinoma uye metastatic cnacer, nezvimwe.
Ropa system: Acute uye isingaperi lymphoblastic leukemia (T lymphomakunze) nezvimwewo.
Imwe kenza: Marignant melanoma, zamu, prostae uye kenza yerurimi, nezvimwe.
Kuvhiya kubvisa ronda rekutanga, asi iyo immunty yakaderera, uye kudzoreredza kunononoka.
Mamota ane metastasis akapararira aisakwanisa kuenderera mberi nekuvhiyiwa.
Iyo yedivi mhedzisiro yechemotherapy uye radiotherapy yakakura kana kusanzwa nekemotherapy uye radiotherapy.
Dzivirira bundu kudzokorora mushure mekuvhiyiwa, chemotherapy uye radiotherapy.
Zvakanakira
1) CAR T maseru 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 chete peptide antigens, asiwo shuga uye lipid antigens, kuwedzera chinangwa chemhando 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 mumuviri kwenguva yakareba.Izvo zvakakosha zvekiriniki kudzivirira bundu kudzoka.