Ukwelashwa kwe-CAR-T: Ikusasa Elithembisayo Lezigameko Zokugula Ezibangelwa Amaseli E-T
Ukwelashwa kwe-Chimeric Antigen Receptor T-cell (CAR-T) kushintshe kakhulu ukwelashwa kwe-B-cell monoansies, kunikeza ukuphulukiswa okuhlala isikhathi eside ngisho nokwelashwa kweziguli eziningi. Bekhuthazwa yile mpumelelo, abacwaningi bagxile ekusetshenzisweni kwe-CAR-T kwe-T-cell monoansies, okuhlanganisa I-T-Cell Lymphomas (TCL) kanye ne-T-cell acute lymphoblastic leukemia (T-ALL). Kodwa-ke, lezi zinhlungu zomdlavuza ze-T-cell ziletha izinselelo ezihlukile zokuthuthukiswa kokwelashwa kwe-CAR-T.
Umdlavuza we-T-cell, obangela ingxenye enkulu yomdlavuza wezingane nowabantu abadala, waziwa ngokuba nolaka kanye nokumelana kwawo nemithi yokwelapha evamile. I-T-ALL kanye ne-TCL zihlukene kakhulu, zinemiphumela emibi ezindaweni ezibuyela emuva noma ezingasasebenzi kahle (r/r), okugcizelela isidingo esiphuthumayo sezinketho ezintsha zokwelapha. Ukwelashwa kwe-CAR-T komdlavuza we-T-cell kuthole ukunakwa okukhulu ngenxa yamandla ayo okuhlinzeka ngesisombululo esiqondisiwe nesisebenzayo.
Inselele isekubonakalisweni okuhlanganyelwe kwezinhloso ze-antigen phakathi kwama-T-cell anobungozi nama-T-cell ajwayelekile, okungaholela "ekubulaweni," lapho amaseli e-CAR-T ebhubhisa khona ama-T-cell anempilo ngengozi. Ngaphezu kwalokho, i-T-cell aplasia, engashiya iziguli zisengozini yokutheleleka, ibeka enye ingozi enkulu. Naphezu kwalezi zithiyo, intuthuko yakamuva yezokwelapha ibonise imiphumela ethembisayo ye-CAR-T ku-T-ALL kanye ne-TCL.
Isibuyekezo sakamuva esishicilelwe ku- Ukuthuthuka Kwegazi iqokomisa izivivinyo eziningana zezokwelapha ezithembisayo. Enye indlela ihilela ukuqondisa i-CD7, iphrotheni ebonakala ebusweni be-T-ALL kanye nama-lymphoma athile e-T-cell. Ezivivinyweni zesigaba sokuqala, ukwelashwa kwe-CAR-T okuqondiswe ku-CD7 kubonise ukusebenza okumangalisayo, kufeza ukuphulukiswa okuphelele ezigulini eziningi. Ngaphezu kwalokho, amasu ahloselwe ukunciphisa "i-fratricide" nokuthuthukisa ukukhiqizwa kwamaseli e-CAR-T avula indlela yokuphumelela kwezokwelapha.
Izilingo zakamuva ziphinde zazama ukuhlela amaseli e-T ukuze kuthuthukiswe ukucaciswa nokuqina kwamaseli e-CAR-T. Isibonelo, ukusetshenziswa kobuchwepheshe be-CRISPR-Cas9 ukuhlosa ama-antigen athile njenge-CD5, i-CD7, kanye ne-TRBC kubonise amandla okuthuthukisa kokubili ukuphepha nokusebenza kahle. Imiphumela yokuqala ikhombisa ukuthi ukwelashwa kwe-CAR-T, uma kuklanywe ngokucophelela, kungaba yisikhali esinamandla sokulwa nomdlavuza wamaseli e-T.
Ngaphezu kwalokho, ukuhlanganisa ukwelashwa kwe-CAR-T nezinye izindlela zokwelapha, njengokufakelwa kwamaseli e-hematopoietic stem (allo-HSCT), kubonise ithemba ekwandiseni ukusinda nokuvimbela ukubuyela emuva. Esivivinyweni sesigaba sesi-2 sokwelashwa kwe-CAR-T okuqondiswe ku-CD7, ama-63.5% eziguli ahlala esesimweni sokululama ngemva kweminyaka emibili, kanti labo abathola i-allo-HSCT bathuthuke kakhulu ekusindeni okungenakho ukuqhubeka (PFS).
Njengoba ucwaningo luqhubeka, isimo sokwelashwa kwe-CAR-T ezifweni zomdlavuza we-T-cell sibonakala sinethemba elikhulu. Nakuba kusenezinselele ezinkulu okumelwe zinqotshwe, okuhlanganisa nokuphatha i-severe cytokine release syndrome (CRS) kanye nobuthi be-neurotoxicity, ukuqonda okuguqukayo kobuchwepheshe be-CAR-T kuyaqhubeka nokwandisa ukusetshenziswa kwayo okungenzeka.
Kwa-BIOOCUS, sizibophezele ekuhlaleni phambili ekuthuthukisweni kokwelashwa kwe-CAR-T futhi sijabule ukunikeza lokhu kwelashwa okuseqophelweni eliphezulu ezigulini emhlabeni jikelele. Njengoba izivivinyo zemitholampilo ziqhubeka nokukhula, sisenethemba lokuthi ukwelashwa kwe-CAR-T ngolunye usuku kuzohlinzeka ngenketho yokwelapha kulabo abahlushwa umdlavuza we-T-cell, okuletha ithemba elisha ezigulini nasemindenini edinga izinketho zokwelapha ezisebenzayo.
Ukuze uthole ulwazi olwengeziwe mayelana nezinhlelo zethu zokwelapha ze-CAR-T, vakashela iwebhusayithi yethu noma uxhumane nethimba lethu lokusekela iziguli.