Ukuphatha Izinkinga Zesikhathi Eside Zokwelashwa Kwe-CAR-T: Ukuqonda Okuvela Kumdlavuza Wemvelo

Ukwelashwa kwamaseli e-Chimeric Antigen Receptor (CAR)-T kushintshe kakhulu ukwelashwa kwezifo ezibangelwa amagciwane egazi, okunikeza ithemba ezigulini ezinezifo ezingalapheki. Kodwa-ke, izinkinga zesikhathi eside ezifana nokutheleleka kanye nomdlavuza wesibili kusalokhu kuyindaba ebalulekile yokuphepha, ngokusho kwesihloko samuva ku- Umdlavuza Wemvelo.

Ukwelashwa kwe-CAR-T kwaqala ukusetshenziswa kabanzi ngenxa yokusebenza kwayo okumangalisayo ezivivinyweni zemitholampilo kanye nezicelo zomhlaba wangempela. Ngenkathi ubuthi obukhulu njenge-cytokine release syndrome (CRS) kanye ne-immune effector cell-associated neurotoxicity syndrome (ICANS) sekuye kwalawuleka ngentuthuko ekunakekelweni okusekelayo, ukuhlaziywa kwakamuva kugcizelela ukwanda kokufa okungaphindeki (NRM) ngenxa yokutheleleka kanye nomdlavuza wesibili phakathi kwabaphenduli be-CAR-T.

Ukuhlaziywa kwe-meta okubandakanya i-7,604 lymphoma kanye I-Multiple Myeloma Iziguli ezithole ukwelashwa kwe-CAR-T ziveze izinga le-NRM eliphelele elingu-6.8%, elihlukahluka ezifweni ezahlukene kanye nezakhiwo ze-CAR-T.Ukutheleleka kwaba yimbangela enkulu yamacala e-NRM, okungahlobene ne Umkhiqizo we-CAR-T uqobo noma isifo esiyisisekelo. Naphezu komthelela omkhulu we-COVID-19 phakathi nesikhathi socwaningo, ukutheleleka ngamagciwane kanye nesikhunta ngakunye kufake isandla ku-20% wokufa okuhlobene nokutheleleka. Lezi zibalo ziyafana nalezo ezibonwe ngemuva kokufakelwa kweseli le-stem le-hematopoietic (auto-HSCT).

Ukuze kuncishiswe lezi zingozi, abacwaningi bagcizelela ukusetshenziswa kwamathuluzi okubikezela njenge-CAR-HEMATOTOX score, ehlola izici ezifana nokugcinwa kwe-hematopoietic kanye nokuvuvukala okuyisisekelo. Lolu hlelo lokulinganisa lusiza ekutholeni iziguli ezisengozini enkulu ezingase zizuze kuma-antibiotic okuvikela aklanyelwe kanye nokuqapha okuqaphile kwamasosha omzimba. Okuphawulekayo ukuthi, i-hematotoxicity ehlobene neseli ethinta amasosha omzimba (ICAHT) ihlobene nesilinganiso se-NRM esiphezulu (14% uma kuqhathaniswa no-4.5% ezimweni ezingezona ezimbi kakhulu).

Umdlavuza wesibili, okuhlanganisa i-myelodysplastic syndromes (MDS), i-acute myeloid leukemia (AML), kanye ne-carcinoma, kungenye into ekhathazayo. Lezi zigameko zomdlavuza zihlotshaniswa kakhulu nokwelashwa okunamandla kwangaphambilini njengokwelashwa ngamakhemikhali kanye ne-auto-HSCT kunomkhiqizo we-CAR-T uqobo. I-Clonal hematopoiesis, eyandulela i-MDS/AML ehlobene nokwelashwa, ibonwe ezigulini ezingafika ku-56% ngaphambi kokufakwa kwe-CAR-T.

Indima yokwelashwa kwe-CAR-T kulezi zimo zomdlavuza isaphenywa. Ngenkathi amacala e-CAR-T ebangelwa yi-CAR-T aqhubeka. I-T-Cell Lymphoma Njengoba kubikiwe, ubudlelwano bembangela busalokhu bungaqinisekile. Kwesinye isenzakalo esiphawulekayo, amazinga aphezulu e-CAR-RNA atholakale ekwelashweni kwe-T-cell lymphoma ngemuva kwe-CAR-T, kodwa ukuhlaziywa kwezakhi zofuzo kwasusa ukufakwa kwe-CAR njengembangela eyinhloko yomdlavuza.

Amasu Okuphatha Izingozi
Ukuze kuthuthukiswe iphrofayili yengozi yenzuzo yokwelashwa kwe-CAR-T, abacwaningi batusa ukungenelela kusenesikhathi ezigulini ezinemigqa embalwa yokwelashwa kwangaphambilini ukuze kuncishiswe ubuthi obuqongelelekayo. Izinhlelo zokuthola amaphuzu okubikezela kanye nokulandelwa kwesikhathi eside kwabamukeli be-CAR-T kungathuthukisa ukuphepha ngokuvumela ukutholakala kusenesikhathi kanye nokuphathwa kwezinkinga.

Lesi sihloko sigcizelela ukubaluleka kokubikwa kwezehlakalo ezimbi ezibanzi ezivivinyweni zemitholampilo nasezindaweni zokubhalisa, ikakhulukazi ezifweni, ezifweni zomdlavuza wesibili, kanye ne-NRM. Imininingwane enjalo izosiza odokotela ukuthi bathuthukise izindlela zokwelapha kanye nezindlela zokukhetha iziguli.

Isiphetho
Nakuba ukwelashwa kwe-CAR-T kuveza amandla okwelapha angenakuqhathaniswa ezifo zomdlavuza wegazi, ukuphatha izingozi zayo zesikhathi eside kubalulekile. Ucwaningo lwesikhathi esizayo kufanele lugxile ekucwengisiseni amathuluzi okubikezela nokuhlola ezinye izindlela zokwelapha zeziguli ezindala noma ezibuthakathaka ezingase zingakubekezeleli kahle ubuthi obuhlobene ne-CAR-T.

Lo msebenzi oyingqayizivele usebenza njengesikhumbuzo sesidingo esiqhubekayo sokulinganisela ukusebenza kahle nokuphepha ekwelashweni okusha, ukuqinisekisa imiphumela emihle kakhulu yeziguli emhlabeni jikelele.