Uphuhliso kwiSifo se-Autoimmune sabantwana: Unyango lweeSeli ze-CAR-T luphilisa iSigulana seLupus

NgoJuni 2023, u-Uresa oneminyaka eli-15 ubudala wafumana unyango lweeseli ze-CAR-T kwiSibhedlele saseYunivesithi yase-Erlangen, nto leyo eyayilulokuqala ukusetyenziswa kolu nyango lutsha lokucothisa ukuqhubela phambili kwe-systemic lupus erythematosus (SLE), isifo esiyingozi sokuzikhusela komzimba. Emva konyaka, u-Uresa uzive esempilweni njengangaphambili, ngaphandle kokuba neengqele ezimbalwa ezincinci.

U-Uresa ngumntwana wokuqala onyangwa i-SLE Unyango lwe-immunotherapy kwiZiko laseJamani le-Immunotherapy (DZI) kwiYunivesithi yase-Erlangen. Impumelelo yolu nyango olucwangcisiweyo ipapashwe kwi-The Lancet.

UGqr. Tobias Krickau, ingcali yamathambo ebantwaneni kwiSebe lezeMpilo yabantwana kunye neMithi yoLutsha kwiSibhedlele sase-Erlangen, uchaze indlela ekhethekileyo yokusebenzisa iiseli ze-CAR-T ukunyanga. Izifo ezichaphazela umzimbaNgaphambili, unyango lwe-CAR-T lwaluvunyiwe kuphela kwiintlobo ezithile zomhlaza wegazi eziphucukileyo.

Emva kokuba onke amanye amayeza engaphumelelanga ukulawula i-SLE eba mandundu ye-Uresa, iqela lophando lijongene nesigqibo esinzima: ngaba ezi seli zomzimba ezicwangcisiweyo kufuneka zisetyenziswe kumntwana onesifo sokuzikhusela komzimba? Impendulo yayingakaze ibonwe ngaphambili, njengoko kungekho mntu wakha wazama unyango lwe-CAR-T kwizifo zokuzikhusela komzimba ebantwaneni ngaphambili.

Unyango lweeseli ze-CAR-T lubandakanya ukukhupha ezinye zeeseli zomzimba zesigulana (iiseli ze-T), ukuzixhobisa ngee-chimeric antigen receptors (i-CAR) kwilabhoratri ekhethekileyo ecocekileyo, uze uzifake kwakhona ezi seli ziguquliweyo kwisigulana. Ezi seli ze-CAR-T zijikeleza egazini, zijolise kwaye zitshabalalise iiseli ze-B ezisebenza nge-autoreactive (ezinobungozi).

Iimpawu zika-Uresa zaqala ekwindla ka-2022, kuquka i-migraines, ukudinwa, iintlungu zamalungu nezihlunu, kunye nokurhawuzelela kobuso—iimpawu eziqhelekileyo ze-lupus. Nangona wayenyangwa kakhulu, imeko yakhe yaba mandundu, yachaphazela izintso zakhe yaza yabangela iingxaki ezinkulu.

Ekuqaleni kuka-2023, emva kokulaliswa esibhedlele izihlandlo ezininzi kunye nonyango, kuquka i-immunosuppressive chemotherapy kunye ne-plasma exchange, imeko ka-Uresa yaba mandundu kangangokuba kwafuneka afumane i-dialysis. Ehlala yedwa kubahlobo nosapho, umgangatho wobomi bakhe wehla kakhulu.

Iqela lezonyango kwiYunivesithi yase-Erlangen, elikhokelwa nguNjingalwazi uMackensen, livumile ukuvelisa nokusebenzisa iiseli ze-CAR-T kwi-Uresa emva kwengxoxo eneenkcukacha. Olu setyenziso lwe-CAR-T ngobubele lwaqalwa phantsi komthetho waseJamani weziyobisi kunye nemigaqo yokusetyenziswa ngobubele.

Inkqubo yonyango lweeseli zeCAR-T e-Erlangen, ekhokelwa nguNjingalwazi uGeorg Schett kunye noNjingalwazi uMackensen, ibinyanga izigulana ezinezifo ezahlukeneyo zokuzikhusela komzimba, kuquka ne-SLE, ukusukela ngo-2021. Impumelelo yabo kwizigulana ezili-15 yapapashwa kwiNew England Journal of Medicine ngoFebruwari 2024, kwaye okwangoku baqhuba uphando lweCASTLE nabathathi-nxaxheba abangama-24, bonke bebonisa ukuphucuka okukhulu.

Ukuze alungiselele unyango lweeseli ze-CAR-T, u-Uresa wenziwa i-chemotherapy engaphantsi ukuze enze indawo yeeseli ze-CAR-T egazini lakhe. Ngomhla wama-26 kuJuni 2023, u-Uresa wafumana iiseli zakhe ze-CAR-T ezenzelwe yena. Kwiveki yesithathu emva konyango, ukusebenza kwezintso zakhe kunye neempawu ze-lupus zaphucuka, kwaye iimpawu zakhe zaphela kancinci kancinci.

Inkqubo yonyango yayibandakanya ukulungelelaniswa okucokisekileyo ukuqinisekisa ukusebenza kakuhle kwe-chemotherapy kunye nokukhuselwa kokusebenza kwezintso okuseleyo. U-Uresa wafumana iziphumo ebezingalindelekanga ezincinci kwaye wakhululwa ngosuku lwe-11 emva konyango.

Ekupheleni kukaJulayi 2023, u-Uresa wabuyela ekhaya, wagqiba iimviwo zakhe, waza wazibekela iinjongo ezintsha zekamva lakhe, kuquka ukuzimela nokufumana inja. Wayevuya kakhulu ukuphinda adibane nabahlobo aze aqhubeke nobomi obuqhelekileyo bobutsha.

UNjingalwazi uMackensen ucacisile ukuba i-Uresa isenalo inani elikhulu leeseli ze-CAR-T egazini lakhe, nto leyo ethetha ukuba udinga ukufakelwa ii-antibody rhoqo ngenyanga de iiseli zakhe ze-B ziphinde ziphile. UGqr. Krickau ugxininise ukuba impumelelo yonyango luka-Uresa ibingenxa yentsebenziswano esondeleyo yamacandelo amaninzi ezonyango kwiZiko laseJamani le-Immunotherapy.

U-Uresa akasadingi mayeza okanye i-dialysis, kwaye izintso zakhe ziphilile ngokupheleleyo. UGqr. Krickau kunye neqela lakhe baceba izifundo ezongezelelweyo zokuphonononga amandla eeseli ze-CAR-T ekunyangeni ezinye izifo ezibangelwa kukuzikhusela komzimba ebantwaneni.

Eli tyala libalulekileyo libonisa amandla onyango lweeseli ze-CAR-T ukubonelela ngoxolo lwexesha elide kwizigulane zabantwana ezinezifo ezinzima zokuzikhusela komzimba ezifana ne-SLE. Impumelelo yonyango lwe-Uresa igxininisa ukubaluleka kokungenelela kwangoko kunye nentsebenziswano yamacandelo amaninzi. Izifundo ezongezelelweyo zeklinikhi ziyafuneka ukuqinisekisa ukhuseleko kunye nokusebenza kakuhle kwexesha elide konyango lweeseli ze-CAR-T kubantwana abanezifo zokuzikhusela komzimba.