Yazisa, Ukuxhobisa, Qhagamshela

Igama lam ndinguPatricia García Rodríguez. Ndingumphandi omncinci kwi-Instituto de Salud Carlos III (eSpain). Ndiyinxalenye yeqela leCellular Biotechnology, eliphantsi kweliso likaGqr. Javier García-Castro. Ndikhuthazekile ukuba ndiphuhlise iindlela ezintsha zonyango umhlaza. Uphando lwam lugxile ekwandiseni unyango olutsha lokunyanga i-osteosarcoma (OS).

Uphando kwiinketho ezintsha zokunyanga umhlaza oneziphumo ezibi lubalulekile. Unyango lweCAR T, uhlobo lonyango lomhlaza, lube neziphumo ezibalaseleyo kumhlaza wegazi kodwa alukasebenzi kwiintlobo zomhlaza oqinileyo kubandakanya i-OS. Kutheni kunzima ukusebenzisa olu nyango lutsha kwi-OS? Kule bhlog, ndiza kuxoxa ngemingeni ekusebenziseni unyango lweCAR T, kunye neendlela zokuzoyisa.

Ukufundisa wethu inkqubo yomzimba ukulwa nomhlaza

Amajoni ethu omzimba ayasikhusela kwizifo. Inezixhobo ezininzi zokuhlasela nantoni na engaziwayo, kuquka nomhlaza. Iiseli ze-T zingabadlali ababalulekileyo kwinkqubo yomzimba yokuzikhusela kwaye umsebenzi wazo kukufumana iiseli ezingalunganga okanye ezosulelekileyo. Ukunikezelwa kolu xanduva, xa befumanisa iseli engaqhelekanga, bayayitshabalalisa ngokukhawuleza. Oku kunciphisa umonakalo kwiiseli eziphilileyo emzimbeni. Umhlaza unokuvala le nkqubo ibavumela ukuba bakhule ngokukhululekileyo.

Nangona kusenokuvakala ngathi yintsomi yenzululwazi, kunokwenzeka ukunika amajoni omzimba wethu “amandla amakhulu” ukuze akwazi ukubona iimpawu kwiiseli zomhlaza aze abulale amathumba ngokunempumelelo ngakumbi. Inkqubo yokubanika obu buchule inzima. Okokuqala, iiseli ze-T zodwa emzimbeni kwinkqubo efana nokunikela ngegazi. Emva koko, kwibhubhoratri, ii-receptors ezenziweyo zongezwa, eziqaphela iiseli zomhlaza. Ezi zamkeli zibizwa ngokuba ziiCAR okanye iChimeric Iantigen Izamkeli. Ngokuxhomekeke kwiziphi iimpawu ezibonwa yiCAR, unyango luya kujolisa ngokwahlukileyo ithumba iintlobo. Xa zibuyiselwa emzimbeni ezi zamkeli zintsha zinika iiseli T amandla okujolisa nokubulala iiseli zomhlaza.

"Ndicinga ukuba ukuphuhlisa unyango olutsha kunokutshintsha indlela ekhoyo ngoku yezigulane ezinomhlaza. Ukuba yinxalenye yeqela kunye nophando olunombono ojolise ekudluliseleni inkqubela phambili kwikliniki lithuba elikhethekileyo lokukhula kunye nokuba negalelo kwisayensi. Yiyo loo nto ndisenza uphando, ukuze ndibonelele ngezisombululo kwizigulana.” – uPatricia García Rodríguez

I-Osteosarcoma kunye ne-CAR T yonyango

Unyango lwe-CAR T alukabinawo nawaphi na amayeza avunyiweyo ngokwezonyango kumathumba aqinileyo. Kukho izizathu ezininzi zoku.

Okokuqala, enye yezona zinto zibalulekileyo zonyango lwe-CAR T luyilo. I-receptor eyenziweyo kufuneka ibe ngqo ekujoliswe kuyo kwithumba. Oku kuthetha ukuba ujoliso kufuneka lubekho kuphela kwiiseli zethumba kwaye hayi kwiiseli ezisempilweni ziqinisekisa ukuba i-CAR T ihlasela kuphela iiseli zethumba. Ngaphandle kwenjongo ethile, i-CAR T inokuhlasela iiseli eziphilileyo, ezikhokelela kwimiphumo emibi. Kunokuba nzima ukufumana into ekujoliswe kuyo kwiithumba eziqinileyo. Izazinzulu sele zisebenza kwisisombululo kule nto. Enye yeengcamango kukusebenzisa ii-receptors ezimbini ezenziweyo endaweni yesinye. Ngale ndlela, i-CAR T cell iyakusebenza kuphela xa idibana neethagethi zombini. Oku kwenza kube nzima ukuba zombini iithagethi ziya kuba kwiiseli eziphilileyo, ngoko kufuneka zibulale kuphela iiseli zomhlaza kwaye zibe neziphumo ebezingalindelekanga ezimbalwa.

Unyango lweCAR T lutofwa egazini lomguli. Kanye egazini, kufuneka ijolise amathumba kunye nayiphi na indawo imastastasis (ukusasaza iiseli zomhlaza). Ingxaki kukuba unyango lusenokungawafumani amathumba. Ngaphambili kwiimvavanyo zeklinikhi, iiseli ze-CAR T ezimbalwa kakhulu zafunyanwa kumathumba, okukhokelela ekusebenzeni kakubi kwe-tumor. Ukoyisa lo mba, iiseli zeCAR T zinokutofwa ngokuthe ngqo kwithumba.

Iiseli ze-CAR T ezilawula ukufikelela kwithumba zidibana nendawo enobutshaba kakhulu. I-OS inommandla okhubaza amajoni omzimba, eneoksijini ephantsi kunye nezondlo ezimbalwa. Iiseli ze-T kufuneka zibe kwindawo enobuhlobo ngakumbi ukuze zisebenze kakuhle. Uphononongo olutsha luyaqhuba ukunciphisa iziphumo zemeko yethumba kunye nokuphucula isiphumo sonyango. Umzekelo, iiseli ze-CAR T zilungisiwe ukuba zingalukhankanyi ucimo oluzenza zingasebenzi. Oku kubanika "amandla ebhetri" ngakumbi kwaye kuthetha ukuba banokusebenza ngcono kwiindawo ezinobutshaba.

Ngokwesiqhelo unyango lweCAR T lwenziwa kwilabhoratri ngeeseli zesigulana. Oku kubangela ukulibaziseka phakathi kwexesha ofuna ukunyanga naxa unako, ngoko ke isigulana sinokungasakwazi ukulufumana unyango ngexesha iCAR T ilungile. Kwakhona, inani elikhulu leeseli ze-CAR T ziyadingeka kwaye inkqubo yokwandisa inani labo iguga iiseli ze-T zibenza bangasebenzi kwaye "baphelelwe" xa besetyenziselwa unyango. Ukusebenzisa iiseli zabaxhasi (iiseli ezisuka komnye umntu ohambelanayo) kunokunciphisa amaxesha okuvelisa. Iiseli zabo zisenokuphelelwa ngamandla ngenxa yokuba umnikezeli akakhange afumane unyango lwangaphambili, ngoko ke iiseli zabo zokhuselo lomzimba zikwimeko engcono. Kukho umngcipheko wokuba umzimba wesigulana uyakwala iiseli zabanikelayo ngoko ubuchule zelabhoratri kunye neendlela zobunjineli bemfuza, njenge CRISPR-case.9, ingasetyenziselwa ukuphucula ukhuseleko kunye nokusebenza kweeseli ze-CAR T zomnikeli.

Nangona kusenokungabonakali kulula, uphando aluyeki. Iiprojekthi zethu kunye nezinye ezininzi zophando sele zisendleleni ukoyisa yonke le miqobo. Ngethemba, kwixesha elizayo, olu nyango lwe-CAR T luya kusetyenziswa ukunyanga i-OS.