CAR-T (Chimeric Antigen Receptor T-cell) ni iki?
Ubwa mbere, reka turebere hamwe ubudahangarwa bw'umubiri bw'umuntu.
Ubudahangarwa bw'umubiri bugizwe n'urusobe rw'uturemangingo, ingirabuzimafatizo, n'ingingo zikorana kugira ngokurinda umubiri. Imwe mu ngirabuzimafatizo z'ingenzi zigize uruhare ni uturemangingo tw'amaraso twera, twitwa kandi leukocytes,biza mu bwoko bubiri bw'ibanze buhuriza hamwe mu gushaka no kurimbura udukoko dutera indwara cyangwaibintu.
Ubwoko bubiri bw'ibanze bwa leukocytes ni:
Fagocytes, uturemangingo turya ibinyabuzima byinjira.
Lymphocytes, uturemangingo dufasha umubiri kwibuka no kumenya ibyateye mbere no gufashaumubiri urabica.
Uturemangingo twinshi dutandukanye dufatwa nk'udukoko twa phagocytes. Ubwoko bukunze kugaragara ni neutrophil,ahanini birwanya bagiteri. Niba abaganga bahangayikishijwe n'ubwandu bwa bagiteri, bashobora gusabaikizamini cy'amaraso kugira ngo harebwe niba umurwayi afite umubare munini wa neutrophils uterwa n'ubwandu.
Ubundi bwoko bwa phagocytes bufite akazi kabwo ko kugenzura ko umubiri usubiza nezaku bwoko runaka bw'umwanzi.
Ubwoko bubiri bwa lymphocytes ni lymphocytes B na lymphocytes T. Lymphocytes zitangiramu igufwa maze bikaguma aho ngaho bigakura bigahinduka uturemangingo twa B, cyangwa bikagenda kuri thymusgland, aho ikura ikaba uturemangingo twa T. Limfosite B na limfosite T bifite uturemangingo twihariyeimikorere: Limfozeti B ni nk'urwego rw'ubutasi rwa gisirikare rw'umubiri, zishakaintego no kohereza ingabo zo kuzikingira. Uturemangingo twa T tumeze nk'abasirikare, tugasenyaAbajura bamenye inzego z'ubutasi.
Ikoranabuhanga rya T cells rya Chimeric antigen receptor (CAR): ni ubwoko bw'uturemangingo twakiraUbudahangarwa bw'umubiri (ACI). Uturemangingo twa T tw'umurwayi tugaragaza CAR binyuze mu kongera kubaka uturemangingoikoranabuhanga, rituma uturemangingo twa T dukora ibikorwa bibasirwa cyane, byica kandi bigakomeza kubaho kurushauturemangingo tw’ubudahangarwa bw’umubiri dusanzwe, kandi dushobora gutsinda uduce duto duto dutuma ubudahangarwa bw’umubiri bugabanuka mu gaceUbudahangarwa bw'umubiri bushobora kwihanganirwa n'ikibyimba no kuvura indwara. Ubu ni uburyo bwihariye bwo kuvura ubudahangarwa bw'umubiri.
Ihame rya CART ni ukuvanamo "uburyo busanzwe" bw'uturemangingo twa T tw'umubiri w'umurwayi.kandi ukomeze gukora igenamigambi rya gene, uteranye muri vitro kugira ngo umenye intego zihariye za kanseri niniintwaro yo kurwanya abakozi "receptor ya antigen ya chimeric (CAR)", hanyuma igashyiramo uturemangingo twa T twahindutsegusubira mu mubiri w'umurwayi, receptors nshya zahinduwe zizaba nk'izishyiraho sisitemu ya radar,ishobora kuyobora uturemangingo twa T mu gushaka no gusenya uturemangingo twa kanseri.
Akamaro ka CART muri BPIH
Bitewe n'itandukaniro riri mu miterere y'aho ikimenyetso cy'imbere mu ngirabuzimafatizo giherereye, CAR yashyizeho ibintu bineibisekuruza. Dukoresha IKARITA igezweho.
1stivuka: Hari igice kimwe gusa cy'ikimenyetso cyo mu ngirabuzimafatizo hamwe n'uburyo ikibyimba kidakora nezaIngaruka zari mbi.
2ndivuka: Hiyongereyeho molekile itera imbaraga ishingiye ku ivuka rya mbere, kandiUbushobozi bw'uturemangingo twa T bwo kwica ibibyimba bwariyongereye.
3rdinkomoko: Hashingiwe ku gisekuru cya kabiri cya CAR, ubushobozi bw'uturemangingo twa T bwo gukumira ikibyimbakwiyongera no guteza imbere apoptosis byarushijeho kuba byiza cyane.
4thivuka: Uturemangingo twa CAR-T dushobora kugira uruhare mu gukuraho uturemangingo twa kanseri binyuze mugukora NFAT ikoreshwa mu gutera interleukin-12 nyuma ya CARimenya antigen yibasiwe.
| Itsinda | Gukangura Igipimo | Ikiranga |
| 1st | CD3ζ | Gukora ku buryo bwihariye kwa selile T, selile T itera uburozi, ariko ntiyashoboraga kwiyongera no kubaho mu mubiri. |
| 2nd | CD3ζ+CD28/4-1BB/OX40 | Ongeraho costimulator, wongere uburozi bw'uturemangingo, ubushobozi bwo gukwirakwiza ibintu bike. |
| 3rd | CD3ζ+CD28/4-1BB/OX40+CD134 /CD137 | Ongeraho ibikoresho 2 byo gusimbuza amashanyarazi, urusheho kunozaubushobozi bwo gukwirakwiza no guhumanya. |
| 4th | Ingirabuzimafatizo zo kwiyahura/Amored CAR-T (12IL) Go CAR-T | Shyiramo gene yo kwiyahura, imbaraga zituma umubiri udashobora kwihagararaho n'izindi ngamba zo kugenzura neza. |
Uburyo bwo kuvura
1) Gutandukanya uturemangingo tw’amaraso: Uturemangingo twa T tw’umurwayi dutandukanywa n’amaraso yo mu gice cy’imbere.
2) Gukora ku buryo uturemangingo twa T dukora: udusaro twa rukuruzi (uturemangingo twa dendritic tw’ubukorano) dutwikiriwe n’uturemangingo tw’umubiri niikoreshwa mu gukora uturemangingo twa T.
3) Guhindura imiterere y'uturemangingo: Uturemangingo twa T twahinduwe mu buryo bwa genetiki kugira ngo tugaragaze CAR mu buryo bwa vitro.
4) Kuzamura: Uturemangingo twa T twahinduwe mu buryo bw'uturemangingo twongerwa mu buryo bwa vitro.
5) Chimiotherapie: Umurwayi abanza kuvurwa na chimiotherapie mbere yo kongera gukoresha selile T.
6) Kongera gutera: Uturemangingo twa T twahinduwe mu buryo bw'uturemangingo twongera kwinjira mu murwayi.
Ibimenyetso
Ibimenyetso byerekana CAR-T
Uruhu rw'ubuhumekero: Kanseri y'ibihaha (Kanseri ntoya, kanseri y'uturemangingo duto,adenocarcinoma), kanseri yo mu nda, n'ibindi.
Uduce tw'igogora: kanseri y'umwijima, igifu n'inkondo y'umura, n'ibindi.
Uduce tw'inkari: Kanseri y'impyiko n'iy'inkari hamwe n'indwara ya kanseri ifata imitsi, n'ibindi.
Uturemangingo tw'amaraso: Leukemia y'amagufwa akabije n'amagufwa adakira (T lymphoma)byakuwemo) n'ibindi.
Izindi kanseri: Melanoma mbi, kanseri y'ibere, kanseri ya prostate n'ururimi, n'ibindi.
Kubagwa kugira ngo haveho igisebe cy'ibanze, ariko ubudahangarwa bw'umubiri ni buke, kandi gukira buhoro.
Ibibyimba bifite ikwirakwira ry’ibibyimba bitashoboraga kubagwa.
Ingaruka mbi za chemotherapy na radiotherapy ni nyinshi cyangwa ntizishobora kubangamira chemotherapy na radiotherapy.
Kurinda ko ikibyimba gishobora kongera kugaruka nyuma yo kubagwa, imiti ivura indwara ya kanseri (chimiotherapie) na radiotherapy.
Ibyiza
1) Uturemangingo twa CAR T tuba twibasiwe cyane kandi dushobora kwica uturemangingo twa kanseri dufite antigen nziza kurushaho.
2) Ubuvuzi bwa selile za CAR-T busaba igihe gito. CAR T isaba igihe gito cyo gupima selile za T kuko ikenera selile nkeya munsi y’ingaruka zimwe zo kuvura. Igihe cyo gupima selile za vitro gishobora kugabanywa kikagera ku byumweru 2, ibyo bikaba byaragabanyije cyane igihe cyo gutegereza.
3) CAR ishobora kumenya antigens za peptide gusa, ndetse na antigens z'isukari na lipide, yongera urwego rw'ingenzi rwa antigens za kanseri. Ubuvuzi bwa CAR T ntibugarukira ku antigens za poroteyine zo mu turemangingo twa kanseri. CAR T ishobora gukoresha antigens z'isukari na lipide zitari proteine zo mu turemangingo twa kanseri kugira ngo imenye antigens mu buryo butandukanye.
4) CAR-T ifite ubushobozi bwo kongera kugaragara mu buryo bwagutse. Kubera ko ahantu hamwe na hamwe hagaragara mu turemangingo twinshi twa kanseri, nka EGFR, gene ya CAR y’iyi antigen ishobora gukoreshwa cyane imaze kubakwa.
5) Uturemangingo twa CAR T dufite ubushobozi bwo kwibuka ubudahangarwa bw'umubiri kandi dushobora kubaho mu mubiri igihe kirekire. Ni ingenzi cyane mu kwirinda ko ikibyimba kizongera kugaruka.