Ukusheshisa Ukulungiswa Kwamaseli E-CAR-T Ukuze Kuthuthukiswe Imiphumela Yesiguli
Ukwelashwa ngamaseli e-CAR-T, ukwelashwa okusha kwe- I-B-Cell Leukemia kanye ne-lymphoma, kuhlolwa kabanzi eminye imidlavuza yegazi, izimila eziqinile, kanye nezinkinga zokuzivikela komzimba. Kodwa-ke, ukwandisa lokhu kwelashwa kube yizinkomba ezintsha kuveza izinselele zezokuthutha, njengoba ukukhiqizwa kwamanje kwamaseli e-CAR-T kungathatha amasonto ama-3-6. Ukubuyekezwa kwamuva ku-I-Lancet Haematology ixoxa ngentuthuko ebalulekile ekukhiqizweni kwamaseli e-CAR-T okuhlose ukwenza lula izinqubo, ukuthuthukisa ikhwalithi yamaseli, kanye nokwandisa ukufinyeleleka kweziguli.
Ngokwesiko, ukulungiswa kwamaseli e-CAR-T kudinga ukuvuselelwa nokwandiswa okukhulu kwamaseli e-in vitro, okungaholela ekukhathaleni kwamaseli kanye nokuncipha kokusebenza kahle kokwelapha. Izinto ezintsha zakamuva, njengezinqubo zokwandiswa okuncishisiwe, izindlela zokungasebenzisi, kanye nokukhiqizwa kwendawo yokunakekelwa, kunikeza ushintsho olusheshayo ngokulawulwa okuncane kwe-in vitro. Lezi zindlela, manje sezisetshenziswa kokubili ezivivinyweni zemitholampilo kanye nakwezentengiselwano. Imikhiqizo ye-CAR-T, kugcizelela ukukhiqizwa kwamaseli e-CAR-T angahlukanisiwe kakhulu futhi angakhathali, okuholela ekwelashweni okungase kuhlinzeke ngemiphumela yokulwa nomdlavuza eqhubekayo.
Ukubuyekezwa kuphinde kugqamise inqubekela phambili ekukhethweni kwangaphambili kwamaseli e-T ukuze kususwe amaseli angafuneki noma acindezela amasosha omzimba, okuthuthukisa amandla okwelapha emikhiqizo ye-CAR-T. Ama-algorithms athuthukisa isikhathi se-leukapheresis ngokusekelwe emiphumeleni yegazi yangaphambi kokwelashwa athuthukisa ukusebenza kahle kwemithombo kanye nokufinyeleleka kwayo.
Izinqubo zokulungiselela i-CAR-T ezisheshayo sezivele zibonisa imiphumela ethembisayo. Izivivinyo zemitholampilo zibonisa ukuthi izikhathi zokukhiqiza ezimfushane zingaholela ekuqineni nasekusebenzeni kahle kwamaseli, ngezifundo eziqhubekayo ezihlola amasu okukhiqiza ashesha kakhulu aletha amaseli e-CAR-T ezigulini ngosuku olulodwa.
Ngaphezu kwezindlela zokunciphisa ukwanda, ubunjiniyela bamaseli obusha bukhulisa ukusebenza kahle kwe-CAR-T. Amasu afaka phakathi ukusetshenziswa kwama-molecule inhibitors amancane ngesikhathi sokukhiqiza ukuze kulondolozwe izinhlobo zememori yamaseli e-T futhi kulwiswane nokukhathala. Isibonelo, ama-AKT inhibitors ahlanganiswa kumaphrothokholi okukhiqiza i-CAR-T, abonisa umsebenzi othuthukisiwe wokulwa nomdlavuza kumamodeli e-leukemia angaphambi kokwelashwa. Ngaphezu kwalokho, amaseli e-CAR-T aklanyelwe ukukhiqiza ama-cytokine avuselela amasosha omzimba, njenge-IL-18, abonisa ukulawulwa komdlavuza okuphakeme emzimbeni kanye nokwanda okuqhubekayo kwamaseli ezivivinyweni zemitholampilo zesigaba sokuqala.
Njengoba isidingo somhlaba wonke sokwelashwa kwe-CAR-T sikhula, lokhu kuthuthuka kuletha amandla okuguqula ukunakekelwa kweziguli, okwenza ukwelashwa okuphumelelayo kutholakale ngokushesha nangezinga elikhulu.