I-CAR-T ye-Systemic Lupus Erythematosus (SLE)

UNksz.C uyisiguli eseselashwe ngempumelelo i-SLE ngokwelashwa kwe-CAR-T. Nansi indaba yakhe.

Ukubuka Konke Kwecala:

UNksz C, owesifazane oneminyaka engu-32 ubudala, ubelokhu elwa nesifo se-systemic lupus erythematosus (SLE) iminyaka emibili. Naphezu kokuthola ukwelashwa okuningana kwendabuko, isimo sakhe sasingalawuleki. Wayenezimpawu ezinzima, okuhlanganisa i-nephritis, ubuhlungu bamalunga, kanye nokuqubuka okuqhubekayo, okwathinta kakhulu izinga lempilo yakhe.

Isimo Sangaphambi Kokwelashwa:

I-SLE kaNksz C yayiphawulwe ngezimpawu ezinzima, okuhlanganisa ubuhlungu obuwohlozayo bamalunga, i-nephritis ephindaphindayo, kanye nokuqubuka okungapheli. Ukuhlolwa kwelabhorethri kwembule ama-antibodies e-DNA anamandla aphezulu kakhulu kanye namazinga aphansi e-C3 kanye ne-C4, okubonisa isifo esisebenzayo. Njengoba ine-Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) engu-16, isimo sikaNksz C sabhekwa njengesibi kakhulu, kanti izindlela zokwelapha ezijwayelekile zokucindezela amasosha omzimba zehlulekile ukuletha impumuzo.

Isinqumo Sokwelashwa Nge-CAR-T:

Ngenxa yesimo sakhe sokungazweli, uNksz C wabhaliswa esivivinyweni somtholampilo sokwelashwa kwamaseli e-CAR-T—ukwelashwa okuguqukile okwasungulwa ekuqaleni komdlavuza othile, kodwa manje sekuhlolwa izifo ezizimele njenge-SLE. Ukwelashwa kwe-CAR-T kusebenza ngobunjiniyela bezakhi zofuzo kumaseli e-T esiguli ukuze kuqondiswe amaseli athile omzimba adlala indima ebalulekile enkambisweni yesifo.

Inqubo Yokwelapha i-CAR-T:

1. Ukukhethwa Kwesiguli: I-SLE kaNkz. C eqinile futhi engaguquki yamenza waba umuntu ofanelekela ukwelashwa nge-CAR-T.

2. Ukulungiselela: Ngaphambi kokuthola amaseli e-CAR-T, uNksz C wenziwa i-chemotherapy conditioning, okuyisinyathelo esijwayelekile sokunciphisa inani lama-lymphocyte akhe akhona nokulungiselela amasosha omzimba wakhe ukumuncwa kwe-CAR-T.

3. Ubunjiniyela be-T-cell: Amaseli e-T kaNksz C aqoqwe futhi aguqulwa elebhu ukuze aveze ama-receptor e-chimeric antigen (CAR) aqondise ama-antigen e-CD19 kanye ne-BCMA. Lawa ma-antigen avame ukutholakala ebusweni bamaseli e-B, adlala indima ebalulekile ekuphazamisekeni kokuzivikela komzimba okubonakala ku-SLE.

4. Ukufakwa Kwamaseli e-CAR-T: Ngemva kokwandiswa nokuhlolwa kwekhwalithi, amaseli e-CAR-T aguquliwe aphinde afakwa emzimbeni kaNkz C. Lokhu kufakwa kwaphawula ukuqala kwesahluko esisha ekulweni kwakhe ne-lupus.

5. Ukuqapha Iziguli Ezilaliswe Esibhedlela: UNksz C waqashwa ngokucophelela izinsuku ezingu-25 ngemuva kokumnika ukuze kuqinisekiswe ukuphepha nokusebenza kahle kokwelashwa. Abasebenzi bezokwelapha baqaphe ngokucophelela noma yiziphi izimpawu zemiphumela emibi, njenge-cytokine release syndrome (CRS), ukusabela okuvamile ekwelashweni kwe-CAR-T.

Imiphumela Yokwelashwa:

1. Impendulo Yesikhashana: Phakathi namasonto amathathu nje kuphela emva kokufakwa, uNksz C wabhekana nokuthuthuka okukhulu kwezimpawu zakhe. Ubuhlungu bakhe bamalunga kanye nokuvuvukala kwaphela, futhi ukuqubuka okuqhubekayo okwakumhlupha iminyaka kwaqala ukuphela. Ukuhlolwa kwelebhu kubonise nokuthi amangqamuzana e-B egazini lakhe asuswe ngempumelelo, okuqinisekisa ukuthi amangqamuzana e-CAR-T ayehlose ngempumelelo izingxenye zomzimba wakhe ezingasebenzi kahle.

2. Ukuhlolwa Kwesikhathi Esimaphakathi (Izinyanga Ezi-3): Ezinyangeni ezintathu ezedlule, umsebenzi wesifo sikaNkk. C wawucishe ungabi khona, kanti amaphuzu akhe e-SLEDAI-2K ehla esuka ku-16 aya ku-2. I-nephritis yakhe, eyayiyinkinga enkulu ngaphambi kokwelashwa, manje yayilawulwa, ngokuncipha okukhulu kwe-proteinuria. Ngaphezu kwalokho, amazinga akhe e-anti-double-stranded DNA antibody ayehlile, futhi amazinga akhe e-C3 kanye ne-C4 aphelele abuyele esimweni esijwayelekile, okubonisa ukubuyiselwa kwebhalansi yomzimba.

3. Imiphumela Yesikhathi Eside (Izinyanga Eziyi-12): Ngemva konyaka ethola ukwelashwa kwe-CAR-T, uNksz C wahlala engenazo izidakamizwa ngaphandle kwezimpawu zokubuyela emuva kwe-SLE. Isimiso sakhe somzimba sokuzivikela sasisindile kancane kancane, futhi ngenkathi amaseli akhe e-B ephinde avuka, awazange abonise noma yimuphi umsebenzi wezifo. Ngaphandle kokubhekana ne-CRS encane, uNksz C akazange abe nemiphumela emibi kakhulu kuyo yonke inqubo yokwelashwa.

Imininingwane eyengeziwe yokwelashwa:

Ukwelashwa kwe-CAR-T kubonise ithemba elikhulu ekwelapheni i-systemic lupus erythematosus (SLE), ikakhulukazi ezigulini ezinezinhlobo ezinzima zesifo ezingamelani nokwelashwa. Izifundo zakamuva zibonisa ukusebenza kwayo, njengoba iziguli eziningi zithola ukuphulukiswa isikhathi eside ngaphandle kwemithi.

Esifundweni esihilela iziguli eziyisishiyagalombili, zonke zibonise ukukhululeka okuphelele kwesifo ngemuva kokuthola ukwelashwa ngamaseli e-CAR-T okuqondiswe kumaseli e-B-positive e-CD19. Ukwelashwa kwaholela ekunciphiseni kwala maseli e-B, anesibopho sokukhiqiza ama-autoantibodies ayingozi ku-SLE. Okubalulekile, ngisho nangemva kokuvuselelwa kwamaseli e-B, lesi sifo asibuyanga, futhi iziguli zakwazi ukugcina izimpendulo ezijwayelekile zomzimba emithini yokugoma. Lokhu kukhomba ukuthi umthelela wokwelashwa kwe-CAR-T uqinile ohlelweni lomzimba, ikakhulukazi ekumiseni ukuhlaselwa okuzenzakalelayo kwe-SLE.

Ucwaningo olulandelela iziguli oluthathe izinyanga ezingaphezu kwe-13 lubonise ukuthi bonke ababambiqhaza babhekane nokwehla okukhulu kokusebenza kwesifo, futhi akukho ukubuyela emuva okubonwe. Ngaphezu kwalokho, ukwelashwa ngokuvamile bekubekezelelwa kahle, kanye nemiphumela emibi emincane efana ne-cytokine release syndrome (CRS) elawulekayo.

Le miphumela ethembisayo isikisela ukuthi ukwelashwa kwe-CAR-T kunganikeza ikhambi elisebenzayo nelihlala isikhathi eside ezigulini ezine-SLE engalapheki, okungenzeka kuqede isidingo sokwelashwa okucindezela amasosha omzimba impilo yonke.