I-CAR-T yeSystemic Lupus Erythematosus (SLE)

UNksz.C sisigulana esifumene unyango lwe-SLE ngempumelelo ngonyango lwe-CAR-T. Nasi ibali lakhe.

Isishwankathelo seTyala:

UNksz C, umfazi oneminyaka engama-32 ubudala, ebesilwa nesifo se-systemic lupus erythematosus (SLE) kangangeminyaka emibini. Nangona wayefumana unyango lwendabuko oluninzi, imeko yakhe ayizange ilawuleke. Wayeneempawu ezinzima, kuquka i-nephritis, iintlungu zamalungu, kunye nokurhawuzelelwa okuqhubekayo, okwachaphazela kakhulu umgangatho wobomi bakhe.

Imeko yangaphambi konyango:

I-SLE kaNksz C yayiphawulwe ziimpawu ezinzima, kuquka iintlungu ezidityanisiweyo zamalungu, i-nephritis ephindaphindayo, kunye nokurhawuzelelwa okungapheliyo. Uvavanyo lwelabhoratri lubonise ii-antibodies ze-DNA ezichasene ne-double-stranded kunye namanqanaba anciphileyo e-C3 kunye ne-C4, nto leyo ebonisa isifo esisebenzayo. Nge-Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) yamanqaku ali-16, imeko kaNksz C yayithathwa njengenzima, kwaye unyango oluqhelekileyo lwe-immunosuppressive aluzange luncede.

Isigqibo soNyango lwe-CAR-T:

Ngenxa yemeko yakhe yokunganyamezelani, uNksz C wabhaliswa kuvavanyo lweklinikhi lonyango lweeseli ze-CAR-T—unyango oluyinguqu ekuqaleni olwaphuhliswa kwiintlobo ezithile zomhlaza, kodwa ngoku luphononongwa kwizifo ezizikhuselayo njenge-SLE. Unyango lwe-CAR-T lusebenza ngobunjineli bezakhi zofuzo kwiiseli ze-T zesigulana ukuze kujoliswe kwiiseli ezithile zomzimba ezidlala indima ebalulekileyo kwinkqubo yesifo.

Inkqubo yoNyango lwe-CAR-T:

1. Ukukhetha Isigulana: I-SLE kaNksz. C enzima nengalawulekiyo yamenza waba ngumntu ofanelekileyo kwi-CAR-T therapy.

2. Ukulungiselela: Ngaphambi kokuba afumane iiseli ze-CAR-T, uNksz C wenziwa i-chemotherapy conditioning, inyathelo eliqhelekileyo lokunciphisa inani lee-lymphocytes zakhe ezikhoyo kunye nokulungiselela amajoni akhe omzimba ukuba afumane i-CAR-T infusion.

3. Ubunjineli beeseli ze-T: Iiseli ze-T zikaNksz. C zaqokelelwa zaza zaguqulwa kwilebhu ukuze ziveze ii-chimeric antigen receptors (CAR) ezijolise kwi-CD19 kunye ne-BCMA antigens. Ezi antigens zihlala zifumaneka kumphezulu weeseli ze-B, ezidlala indima ebalulekileyo kwi-immune dysregulation ebonwa kwi-SLE.

4. Ukufakwa kweeSeli zeCAR-T: Emva kokwandiswa novavanyo lomgangatho, iiseli ze-CAR-T eziguquliweyo zafakwa emzimbeni kaNks. C. Olu tyando luphawule ukuqala kwesahluko esitsha kumlo wakhe wokulwa ne-lupus.

5. Ukubeka iliso kwizigulane ezilaliswayo: UNksz C ujongwe ngononophelo kangangeentsuku ezingama-25 emva kokufakwa kweyeza ukuqinisekisa ukhuseleko nokusebenza kakuhle konyango. Abasebenzi bezonyango bajonge ngokusondeleyo naziphi na iimpawu zeziphumo ebezingalindelekanga, ezifana ne-cytokine release syndrome (CRS), impendulo eqhelekileyo kunyango lwe-CAR-T.

Iziphumo Zonyango:

1. Impendulo yexesha elifutshane: Kwiiveki ezintathu nje emva kokufakwa, uNksz C wafumana ukuphucuka okukhulu kwiimpawu zakhe. Iintlungu zakhe zamalungu kunye nokudumba kwaphela, kwaye amaqhuqhuva angapheliyo awayemkhathaza iminyaka aqala ukuphela. Uvavanyo lwelabhoratri lukwabonise ukuba iiseli ze-B egazini lakhe zazisusiwe ngempumelelo, nto leyo eqinisekisa ukuba iiseli ze-CAR-T zazijolise ngempumelelo kumacandelo angasebenzi kakuhle kwenkqubo yakhe yomzimba yokuzikhusela.

2. Uvavanyo lweXesha eliPhakathi (Iinyanga ezi-3): Kwisithuba seenyanga ezintathu, umsebenzi wesifo sikaNksz C wawuphantse ungabikho, amanqaku akhe e-SLEDAI-2K ehla ukusuka kwi-16 ukuya kwi-2. I-nephritis yakhe, eyayixhalabisa kakhulu ngaphambi konyango, ngoku yayilawulwa, kunye nokwehla okukhulu kwe-proteinuria. Ukongeza, amanqanaba akhe e-anti-double-stranded DNA antibody ayehlile, kwaye amanqanaba akhe e-C3 kunye ne-C4 abuyele kwisiqhelo, nto leyo ebonisa ukubuyiselwa kokulinganisela komzimba.

3. Iziphumo zexesha elide (iinyanga ezili-12): Emva konyaka efumene unyango lwe-CAR-T, uNksz C wahlala engenazo iziyobisi ngaphandle kwempawu zokubuyela kwi-SLE. Inkqubo yakhe yomzimba yokuzikhusela yayisele ibuyele esiqhelweni kancinci kancinci, kwaye nangona iiseli zakhe ze-B zaziphinde zavela, azizange zibonise ntshukumo ibangela izifo. Ngaphandle kokuba ne-CRS encinci, uNksz C akazange abe nemiphumo emibi kakhulu kuyo yonke inkqubo yonyango.

Idatha engakumbi yonyango:

Unyango lwe-CAR-T lubonise ithemba elikhulu ekunyangeni i-systemic lupus erythematosus (SLE), ingakumbi kwizigulana ezineentlobo ezinzima zesifo ezinganyangekiyo kunyango. Izifundo zakutshanje zibonisa ukusebenza kwayo, kwaye izigulana ezininzi zifumana ukuphumla ixesha elide ngaphandle kwamayeza.

Kwisifundo esibandakanya izigulana ezisibhozo, zonke zibonakalise ukukhululeka ngokupheleleyo kwisifo emva kokufumana unyango lweeseli ze-CAR-T olujolise kwiiseli ze-B ezine-CD19. Olu nyango lukhokelele ekuphelelweni kwezi seli ze-B, ezinoxanduva lokuvelisa ii-autoantibodies eziyingozi kwi-SLE. Okubalulekileyo kukuba, nasemva kokuvuselelwa kweeseli ze-B, esi sifo asizange sibuye, kwaye izigulana zikwazile ukugcina iimpendulo eziqhelekileyo zomzimba kwiigonyo. Oku kubonisa indlela unyango lwe-CAR-T oluhlala luhleli ngayo kwimpembelelo yomzimba, ngakumbi ekumiseni uhlaselo lwe-autoimmune oluphawu lwe-SLE.

Uphononongo olulandelela izigulana oluthathe iinyanga ezili-13 lubonise ukuba bonke abathathi-nxaxheba baye bancipha kakhulu ekusebenzeni kwesi sifo, kwaye akukho kuphinda kubonwe ukuphinda kubuye. Ngaphezu koko, unyango beluqhele ukunyanyekelwa kakuhle, kwaye iziphumo ebezingalindelekanga ezincinci ezifana ne-cytokine release syndrome (CRS) ziyalawuleka.

Ezi ziphumo zithembisayo zibonisa ukuba unyango lwe-CAR-T lunokubonelela ngesisombululo esisebenzayo nesihlala ixesha elide kwizigulane ezine-SLE enganyangekiyo, nto leyo enokuphelisa isidingo sonyango lokunciphisa amajoni omzimba ubomi bonke.