March 2022: Indlela yokuguquguquka Ukwelashwa kwe-CAR-T Cell inamandla okugumbuqela lokho osekuyi-axiom yezokwelapha: ukuthi umphumela ophawulekayo wokwelashwa kumathumba ufika ngenani lezingozi ezinkulu ekuphepheni kwesiguli.
Iziguli zelashwe ngenguqulo eshintshwe kancane ye-CAR-T egunyaziwe zithole izinzuzo eziqhathaniswa nezifundo zangaphambili, kodwa ngaphandle kwemiphumela emibi evamile ngezinye izikhathi ethumela iziguli esibhedlela futhi kudinge ukwelashwa okwengeziwe okumba eqolo.
Ngokwemininingwane ekhishwe muva nje, leli cala libhalise abantu abangama-25 kuphela eChina. Ochwepheshe bakholelwa ukuthi uma okutholakele kungaphindwa, ukuhlola kancane kwamangqamuzana kungenza i-CAR-T iphephe futhi itholakale kalula.
“Lokhu kubonakala kuthembisa kakhulu,” kusho uJill O'Donnell-Tormey, oyi-CEO yeCancer Research Institute, okuyinhlangano engenzi nzuzo. “Ngokusobala, kusekuqaleni komdlalo, kodwa impendulo abayitholile kubantu abangu-25 abababonile kuze kube manje iyamangaza.”
Ukwelashwa kwe-CAR-T kwenziwa ngokuthatha amangqamuzana omzimba esiguli, ngokuwaguqula ukuze aqondise izimila, bese ejova ngezinto ezikhuthaza izivikelo zemvelo zomzimba ukuthi zihlanganyele empini. Ososayensi bagxile esigabeni sokugcina senqubo yokudala umuthi ophephile.
Baqala nge-Novartis' Kymriah, eyagunyazwa ukwelapha izinhlobo ezimbili zezifo ezibulalayo zegazi, base bezakhela ezabo izifaniso, ngayinye ithungwe ngokulandelana okuhluke kancane kwe-amino acid. Babone okuthile okuthakazelisayo lapho bezama lezi zinguquko kumagundane: Enye ye-CAR-Ts eguquliwe yakwazi ukubulala amangqamuzana omdlavuza ngaphandle kokwenza impendulo yokuzivikela komzimba enomkhuhlane noma ukukhiqiza ukuvuvukala kobuchopho, okuyimiphumela emibili evame kakhulu yokwelashwa kwamaseli.
Iphinde yaphumelela ekuhlolweni kwabantu. I-Kymriah eshintshiwe akubanga namacala amakhulu e-cytokine release syndrome, i-immune flareup njalo kumaseli e-CAR-T, futhi akukho neurotoxicity, ngokusho kocwaningo olushicilelwe ku-Nature Medicine. Ocwaningweni olushicilelwe lukaNovartis, nokho, ngaphezu kwesigamu seziguli zakhululwa i-cytokine, futhi cishe ingxenye yesine yayinezinkinga zemizwa.
UDkt. Si-Yi Chen, uprofesa we-immunology e-University of Southern California kanye nombhali oyinhloko waleli phepha, uthe, “Kusimangaze kakhulu lokho. Abasebenza noChen nabo bamangala.
I-CAR-T eguquliwe ibukeke sengathi ithole indawo emnandi ye-immunological, eheha ama-cytokines anele ukuthi abe nomthelela kumdlavuza ngaphandle kokudala umonakalo. Nokho, akucaci ukuthi kungani lokhu kwenzeka. Kungenzeka ukuthi ama-CAR-T anelayisense afana ne-Kymriah ne-Gilead Sciences' Yescarta anamandla kakhulu, nokuthi ukwelapha okuncane kungafinyelela imiphumela efanayo ngengozi encane. Kungase futhi kube yindaba yenhlanhla.
UDkt. Loretta Nastoupil, induna ye i-lymphoma eMnyangweni we-MD Anderson Cancer Center e-Houston, uthe, "Ngizobheka lokhu ngokuqapha, noma ngethemba elicophelelayo." “Kuzobaluleka kakhulu ukuqonda izinqubo ezisebenza ngayo.
Kuphinde kube nodaba lokusebenza isikhathi eside, okudlulela ngale kwesayensi eyisisekelo. Ama-CAR-T avunyelwe ngokuvamile aholela ekukhishweni kwesikhathi eside. UDkt. Michel Sadelain, udokotela wamasosha omzimba esikhungweni somdlavuza weSikhumbuzo Sloan Kettering, uthe isu likaChen libonakala liphephile esikhathini esifushane, kodwa kufanele kubonakale ukuthi imiphumela izohlala isikhathi eside yini.
"Inkinga ukuthi uma wenza buthaka i-CAR, lokho kuhle kakhulu uma wehlisa ukukhiqizwa kwe-cytokine, kodwa unganciphisa umphumela wokwelapha?" Kuchaza uSadelain. “Nakhu lapho kunombuzo omkhulu. “Isikhathi kuphela esiyosho,” kusho umbalisi.
Ngaphandle kwalokho kukhathazeka, ithemba le-CAR-T ephephile linganweba kakhulu ukufinyelela ekwelashweni okutholakala kuphela ezikhungweni ezinkulu zomdlavuza. Imiphumela emibi yokwelashwa ngokuvamile idinga ukunakekelwa okukhethekile kanye nekhono elingafinyeleleki ezibhedlela zomphakathi, okukhawulela inani leziguli ezingelashwa.
Bese kuba nenani. Izindleko zokwelashwa kwe-CAR-T zingaphezulu kuka-$370,000 ukwelashwa ngakunye, nakuba lokho kungabandakanyi izindleko zokulaliswa esibhedlela noma imithi yokucindezela amasosha omzimba. Ngokuka-Avery Posey, i immunotherapy Umcwaningi eNyuvesi yasePennsylvania, izindleko zokugcina ezimweni ezimbi kakhulu zivame ukusondela ku-$1 million.
"Lokho izakhamuzi zasePenn ezikubiza ngokuthi 'i-CAR-Tastrophy,'" u-Posey washo ngengxube yemiphumela emibi ye-immunological kanye neurotoxicity.
