Ukuphumelela kwiZifo eziZimelayo zaBantwana: Unyango lweeseli ze-CAR-T Unyanga iLupus isigulana
NgoJuni ka-2023, u-Uresa oneminyaka eli-15 ubudala wafumana unyango lweseli ye-CAR-T kwiSibhedlele seYunivesithi yase-Erlangen, ephawula ukusetyenziswa kokuqala kolu nyango lunolutsha ukuze lucothise ukuqhubela phambili kwe-systemic lupus erythematosus (SLE), isifo esiyingozi esizimelayo. Emva konyaka, u-Uresa uziva esempilweni njengakuqala, ngaphandle kwengqele engephi.
Uresa ngumntwana wokuqala onyangelwe i-SLE nge-immunotherapy kwiZiko laseJamani leYunivesithi yase-Erlangen ye-Immunotherapy (DZI). Impumelelo yolu nyango lomntu ngamnye ipapashwe kwiLancet.
UGqr. Tobias Krickau, i-rheumatologist yabantwana kwiSibhedlele seYunivesithi yase-Erlangen yeSebe leZibhedlele zePediatrics kunye ne-Adolescent Medicine, ichaze into ekhethekileyo yokusebenzisa iiseli ze-CAR-T ukunyanga izifo ezizimele. Ngaphambili, unyango lwe-CAR-T lwaluvunyiwe kuphela kwii-cancer ezithile eziphezulu zegazi.
Emva kokuba onke amanye amayeza awaphumelelanga ekulawuleni i-SLE eyandayo ye-Uresa, iqela lophando lijongene nesigqibo esinzima: ngaba ezi seli ze-immune zenziwe ukuba zisetyenziswe kumntwana onesifo esizimelayo? Impendulo yayingazange ibonwe ngaphambili, njengoko kungekho mntu wazama unyango lwe-CAR-T kwizifo zabantwana ezizimelayo ngaphambili.
Unyango lweeseli ze-CAR-T lubandakanya ukukhupha ezinye zeeseli ze-immune zesigulane (iiseli ze-T), zixhotyiswe nge-chimeric antigen receptors (CAR) kwilebhu ekhethekileyo ecocekileyo, kwaye emva koko iphinda ibuyisele ezi seli eziguquliweyo kwisigulane. Ezi seli ze-CAR-T zijikeleza egazini, zijolise kwaye zitshabalalise iiseli ze-B ezizenzekelayo (eziyingozi).
Iimpawu ze-Uresa zaqala ekwindla ye-2022, kuquka i-migraines, ukukhathala, intlungu edibeneyo kunye nemisipha, kunye ne-rash ebusweni-impawu eziqhelekileyo ze-lupus. Phezu kwako nje unyango oluqatha, imeko yakhe yaba mandundu, yachaphazela izintso yaza yabangela iingxaki ezinzima.
Ekuqaleni kuka-2023, emva kokulaliswa esibhedlele izihlandlo ezininzi kunye nonyango, kubandakanywa nechemotherapy ye-immunosuppressive kunye nokutshintshiselana ngeplasma, imeko ka-Uresa iye yaba maxongo kangangokuba wayefuna i-dialysis. Ekubeni wayeyedwa kubahlobo nakusapho, umgangatho wobomi bakhe wehla.
Iqela lezonyango kwiYunivesithi yase-Erlangen, ekhokelwa nguNjingalwazi uMackensen, yavuma ukuvelisa nokusebenzisa iiseli ze-CAR-T ze-Uresa emva kweengxoxo ezicacileyo. Oku kusetyenziswa ngovelwano kunyango lwe-CAR-T kwaqalwa phantsi komthetho weziyobisi waseJamani kunye nemigaqo yokusetyenziswa kwemfesane.
Inkqubo ye-CAR-T ye-cell therapy e-Erlangen, ekhokelwa nguNjingalwazi uGeorg Schett kunye noProfesa Mackensen, uye waphatha izigulane ezinezifo ezahlukeneyo ze-autoimmune, kuquka i-SLE, ukususela ngo-2021. Impumelelo yabo kunye nezigulane ze-15 yapapashwa kwiNew England Journal of Medicine ngoFebruwari. Ngo-2024, kwaye ngoku baqhuba isifundo se-CASTLE kunye nabathathi-nxaxheba be-24, bonke babonisa ukuphuculwa okuphawulekayo.
Ukulungiselela unyango lweeseli zeCAR-T, u-Uresa wenziwa ichemotherapy yedosi ephantsi ukwenza indawo yeeseli zeCAR-T ezisegazini lakhe. Nge-26 kaJuni ka-2023, u-Uresa wafumana iiseli zakhe zeCAR-T. Kwiveki yesithathu emva kokunyangwa, ukusebenza kwezintso kunye nezalathisi zelupus ziye zaphucuka, kwaye neempawu zakhe ngokuthe ngcembe zanyamalala.
Inkqubo yonyango yayibandakanya ukulungelelaniswa ngokucophelela ukuqinisekisa ukusebenza kakuhle kwe-chemotherapy kunye nokukhuselwa komsebenzi wezintso eziseleyo. I-Uresa ifumene iziphumo ebezingalindelekanga ezincinci kwaye yakhutshwa ngomhla we-11 emva konyango.
Ekupheleni kukaJulayi ka-2023, u-Uresa wabuyela ekhaya, wagqiba iimviwo zakhe, kwaye wazibekela iinjongo ezintsha ngekamva lakhe, kuquka ukuzimela kunye nokufumana inja. Wayekuvuyela ukuphinda anxulumane nabahlobo aze aqalise ubomi obuqhelekileyo bobutsha.
Unjingalwazi uMackensen uchaze ukuba i-Uresa isenenani elibalulekileyo leeseli ze-CAR-T egazini lakhe, nto leyo ethetha ukuba kufuneka atofelwe inyanga nenyanga i-antibody de iiseli zakhe ze-B ziphinde ziphile. UGqr. Krickau wagxininisa ukuba ukuphumelela kwonyango lwe-Uresa kwakungenxa yentsebenziswano esondeleyo yeendlela ezininzi zonyango kwiZiko laseJamani le-Immunotherapy.
I-Uresa ayisafuni naliphi na iyeza okanye i-dialysis, kwaye izintso zakhe ziye zachacha ngokupheleleyo. UGqr. Krickau kunye neqela lakhe baceba izifundo ezongezelelweyo zokuhlola amandla e-CAR-T iiseli ekuphatheni ezinye izifo ze-autoimmune zabantwana.
Le meko iphawulekayo ibonisa amandla onyango lweeseli ze-CAR-T ukubonelela ukuxolelwa kwexesha elide kwizigulane zabantwana abanezifo ezinzima ze-autoimmune ezifana ne-SLE. Impumelelo yonyango luka-Uresa ibalaselisa ukubaluleka kokungenelela kwangethuba kunye nentsebenziswano kwiinkalo ezininzi. Izifundo ezongezelelweyo zeklinikhi ziyafuneka ukuze kuqinisekiswe ukhuseleko lwexesha elide kunye nokusebenza kakuhle kwe-CAR-T yonyango lweseli kubantwana abanezifo ezizimelayo.