CAR-T ni iki (Chimeric Antigen Receptor T-selile)?
Ubwa mbere, reka turebe sisitemu yumubiri yumuntu.
Sisitemu yubudahangarwa igizwe nurusobe rw'utugingo ngengabuzima, ingirangingo, n'ingingo zikoranakurinda umubiri.Imwe mu ngirabuzimafatizo zikomeye zirimo selile yera, nayo yitwa leukocytes,biza muburyo bubiri bwibanze buhuza gushaka no gusenya ibinyabuzima bitera indwara cyangwaibintu.
Ubwoko bubiri bwibanze bwa leukocytes ni:
Phagocytes, selile zihekenya ibinyabuzima byinjira.
Lymphocytes, selile zemerera umubiri kwibuka no kumenya abateye mbere no gufashaumubiri ubatsemba.
Umubare wingirabuzimafatizo zitandukanye zifatwa nka fagocytes.Ubwoko bukunze kugaragara ni neutrophil,irwanya cyane cyane bagiteri.Niba abaganga bahangayikishijwe n'indwara ya bagiteri, barashobora gutumizakwipimisha amaraso kugirango harebwe niba umurwayi afite ubwiyongere bwa neutrophile buterwa n'ubwandu.
Ubundi bwoko bwa fagocytes bufite akazi kayo kugirango umenye neza ko umubiri witabira nezaKuri Ubwoko Bwihariye.
Ubwoko bubiri bwa lymphocytes ni B lymphocytes na Lymphocytes T.Lymphocytes itangiramumagufa yamagufa hanyuma ugumeyo kandi ukuze muri selile B, cyangwa bagenda kuri thymusgland, aho bakura muri selile T.Lymphocytes B na Lymphocytes T zitandukanyeimikorere: B lymphocytes B isa na sisitemu yubutasi ya gisirikare yumubiri, ishakisha ibyabointego no kohereza kwirwanaho kugirango ubafunge.T selile ni nkabasirikare, basenya Uwitekaabateye sisitemu yubutasi yamenye.
Chimeric antigen reseptor (CAR) T tekinoroji ya selile: ni ubwoko bwimikorere ya selileimmunotherapy (ACI).Akagari ka T k'umurwayi kagaragaza CAR binyuze mu kwiyubakatekinoroji, ituma ingirabuzimafatizo T ikora cyane, yica kandi ikomeza kurutaingirabuzimafatizo zisanzwe, kandi zirashobora gutsinda immunosuppressive microen ibidukikije yaikibyimba no kumena abashyitsi kwihanganira ubudahangarwa.Ubu ni uburyo bwihariye bwo kwirinda indwara - kuvura ibibyimba.
Ihame rya CART ni ugukuramo "verisiyo isanzwe" yingirabuzimafatizo yumurwayi wenyinehanyuma ukomeze gene injeniyeri, ikoranyirize muri vitro kubibyimba byihariye bya bininiintwaro ya antipersonnel "reseptor chimeric antigen reseptor (CAR)", hanyuma ushiremo selile T yahinduwegusubira mumubiri wumurwayi, reseptor nshya zahinduwe zizaba nko gushiraho sisitemu ya radar,ikaba ishobora kuyobora selile T kumenya no gusenya selile.
Ibyiza bya CART kuri BPIH
Bitewe nuburyo butandukanye muburyo bwa signal internacellular signal domaine, CAR yateje imbere bineibisekuruza.Dukoresha ibisekuru bigezweho CART.
1stigisekuru: Hariho ibimenyetso bimwe gusa byerekana ibimenyetso no kubuza ibibyimbaIngaruka zari mbi.
2ndigisekuru: Wongeyeho molekile ikangura-ishingiye ku gisekuru cya mbere, naubushobozi bwa selile T yo kwica ibibyimba byatejwe imbere.
3rdigisekuru: Ukurikije igisekuru cya kabiri cya CAR, ubushobozi bwa selile T yo kubuza ikibyimbagukwirakwizwa no guteza imbere apoptose byateye imbere cyane.
4thigisekuru: CAR-T selile irashobora kugira uruhare mugukuraho umubare wibibyimba bygukora ibikorwa byo kwandikirana NFAT kugirango itere interleukin-12 nyuma ya CARamenya intego ya antigen.
| Igisekuru | Kubyutsa Ikintu | Ikiranga |
| 1st | CD3ζ | Gukora T selile yihariye, cytotoxic T selile, ariko ntishobora gukwirakwira no kubaho imbere mumubiri. |
| 2nd | CD3ζ + CD28 / 4-1BB / OX40 | Ongeraho Costimulator, utezimbere uburozi bwa selile, ubushobozi buke bwo gukwirakwiza. |
| 3rd | CD3ζ + CD28 / 4-1BB / OX40 + CD134 / CD137 | Ongeramo imyambarire 2, utezimbereubushobozi bwo gukwirakwiza n'uburozi. |
| 4th | Kwiyahura gene / Amored CAR-T (12IL) Genda CAR-T | Kwinjiza gene yo kwiyahura, garagaza ibintu birinda umubiri hamwe nizindi ngamba zifatika zo kugenzura. |
Uburyo bwo kuvura
1) Akagari k'amaraso yera yitaruye: Uturemangingo T tw’umurwayi twitaruye amaraso ya periferiya.
2) T gukora T selile: amasaro ya magnetique (selile dendritic selile) yashizwemo na antibodies niikoreshwa mu gukora T selile.
3) Kwimura: T selile ikorwa genetike kugirango igaragaze CAR muri vitro.
4) Amplification: T selile yahinduwe genetike yongerewe imbaraga muri vitro.
5) Chimiotherapie: Umurwayi yabanje kuvurwa na chimiotherapie mbere yuko T selile yongera.
6) Kongera gushiramo: T selile yahinduwe genetike igaruka mumurwayi.
Ibyerekana
Ibyerekana CAR-T
Sisitemu y'ubuhumekero: Kanseri y'ibihaha (Kanseri ntoya, kanseri y'udukoko,adenocarcinoma), kanseri ya nasofarynx, nibindi.
Sisitemu y'ibiryo: Umwijima, igifu na kanseri yibara, nibindi.
Sisitemu yinkari: Impyiko na kanseri ya adrenal na cnacer metastatic, nibindi
Sisitemu yamaraso: Lymphoblastique ikaze kandi idakira (T lymphoma T)ukuyemo) n'ibindi.
Izindi kanseri: Melanoma mbi, amabere, prostae na kanseri y'ururimi, nibindi
Kubaga kugirango ukureho ibisebe byibanze, ariko ubudahangarwa buri hasi, kandi kwisubiraho biratinda.
Ibibyimba bifite metastasis ikwirakwizwa bidashobora gukomeza kubagwa.
Ingaruka mbi ya chimiotherapie na radiotherapi nini cyangwa itumva imiti ya chimiotherapie na radiotherapi.
Irinde ikibyimba kongera kubaho nyuma yo kubagwa, chimiotherapie na radiotherapi.
Ibyiza
1) CAR T selile yibasiwe cyane kandi irashobora kwica selile yibibyimba hamwe na antigen yihariye.
2) Ubuvuzi bwa CAR-T busaba igihe gito.CAR T isaba igihe gito kumuco T selile kuko isaba selile nkeya muburyo bumwe bwo kuvura.Umuco wa vitro cycle urashobora kugabanywa kugeza kumyumweru 2, ibyo bikaba byaragabanije cyane igihe cyo gutegereza.
3) CAR ntishobora kumenya antigene ya peptide gusa, ariko kandi irashobora kumenya isukari na antipine ya lipide, ikagura intego ya antigene yibibyimba.Ubuvuzi bwa CAR T nabwo ntibugarukira kuri poroteyine antigene ya selile yibibyimba.CAR T irashobora gukoresha isukari hamwe na lipide itari proteyine ya selile yibibyimba kugirango imenye antigene mubipimo byinshi.
4) CAR-T ifite ubugari runaka - imyororokere yimyororokere.Kubera ko imbuga zimwe zigaragarira mu ngirabuzimafatizo nyinshi, nka EGFR, gene CAR kuri iyi antigen irashobora gukoreshwa cyane iyo yubatswe.
5) CAR T selile ifite imikorere yibikorwa byumubiri kandi irashobora kubaho mumubiri igihe kirekire.Ni ingirakamaro cyane mubuvuzi kugirango ikibyimba kitazongera kubaho.