Ukulwa ne-Hepatocellular Carcinoma nge-Bioocus GPC3 CAR-T Therapy

Isizinda Sesiguli

UPawan, umuntu ozinikele waseNdiya, watholakala enesifo sesibindi esingamahlalakhona esiyinkimbinkimbi yi-multifocal hepatocellular carcinoma (HCC) ngo-Agasti 2024. Lapho eneminyaka engu-67 ubudala lapho exilongwa (ehlanganisa iminyaka engu-68 ngesikhathi sokwelashwa), wabhekana nesifo esibi esinezilonda eziningi zesibindi, izimpawu eziphakeme zesimila njenge-AFP ne-PIVKA-II, i-anemia, ukungasebenzi kahle kwe-enzyme yesibindi, kanye nokuguqulwa kwamathambo kamuva. Naphezu kokuthola i-transarterial radioembolization (TARE), i-transarterial chemoembolization (TACE), i-immunotherapy (Atezolizumab + Bevacizumab, Tremelimumab + Durvalumab), kanye nezindlela zokwelapha eziqondiwe (Lenvatinib, Cabozantinib, Regorafenib), isifo sakhe saqhubeka. Ukuhlolwa kwezakhi zofuzo kwembule izinguquko ku-TP53, KRAS, CDKN2A, CTNNB1, kanye ne-ARID1A, ngokubonakaliswa okuphansi kwe-PD-L1 kanye nokungalungi kwe-HRD, okubonisa impendulo elinganiselwe kwezinye izithiyo. Efuna izixazululo ezithuthukisiwe, uPawan wathunyelwa eSibhedlela Somdlavuza saseTianjin ngeBioocus ukuze athole ukwelashwa kwethu kwe-autologous GPC3 CAR-T ngaphansi kwenombolo yokwelashwa P1544.

Uhambo Lokwelapha

Ukwelashwa kwe-CAR-T kukaPawan kwaqala nge-leukapheresis ngo-Agasti 11, 2025, kwalandelwa ukukhiqizwa kanye nokufakwa ngoSepthemba 2, 2025. Wathola umthamo wamaseli e-CAR-T angu-4.73 × 10^8, eqondiswe ku-GPC3, uphawu oluvezwe ngokweqile ku-HCC. Ukulungiswa kokufakwa ngaphambi kokufakwa kwakuhlanganisa i-fludarabine kanye ne-cyclophosphamide ukuze kuthuthukiswe ukufakwa. Ngemva kokufakwa, igazi lakhe elingaphandle laqashwa ukuze kutholakale ukwanda kwe-CAR-T ezinsukwini 4 (D4), 7 (D7), 10 (D10), kanye no-12 (D12).

• D4 (Septhemba 6, 2025):Amaseli e-CAR-T ku-5.15% wamaseli e-CD3+ T (inani eliphelele: 9.27 × 10^6/L), okubonisa ukufakwa kokuqala.
• D7 (Septhemba 9, 2025):Kufinyelele ku-3.97% (6.12 × 10^7/L), okubonisa ukwanda okusebenzayo.
• D10 (Septhemba 12, 2025):04% (9.07 × 10^6/L).
• D12 (Septhemba 14, 2025):Kuzinze ku-2.82% (2.26 × 10^7/L), ngamaseli e-T aphelele ku-5.4 × 10^9/L, i-CD3+ ku-14.87%, amaseli e-T ayingozi e-CD8+ aphezulu ku-77.88%, kanye nama-subset e-CAR-T alinganisiwe (isb., 2.46% CD8+CARGPC3+/CD8+).

Ngesikhathi sokulaliswa esibhedlela kusukela mhla ziyi-11 kuNcwaba kuya kuMandulo 15, 2025, uPawan wabhekana nemiphumela emibi emincane, okuhlanganisa umkhuhlane ophansi (kufika ku-38.5°C), ukukhathala, kanye nokwenyuka kwama-enzyme esibindi okwesikhashana, okwaphathwa ngokusekela ngaphandle kwe-cytokine release syndrome enzima (ibanga le-CRS 1) noma ubuthi be-neurotoxicity. Izimpawu ezibalulekile zahlala zizinzile, kanti ukunakekelwa okusekelayo kwakuhlanganisa nemithi yokulwa nokutheleleka, ukudla okunomsoco, kanye nokuqapha izinkinga ezifana ne-ascites.

Imiphumela Evelele

Ukwandiswa kwe-CAR-T, nakuba kuncane, kubonise ukuphikelela kanye nomsebenzi wokulwa nomdlavuza, okuhambisana nezimpawu zesimila ezizinzile futhi akukho ukuqhubeka okusheshayo ekuthathweni kwezithombe. Icala likaPawan lihambisana nempumelelo ye-Bioocus ku-GPC3 CAR-T ye-HCC, lapho ngisho nokuphikelela kwezinga eliphansi kungaholela ekuphenduleni okuhlala isikhathi eside ezigulini ezingakwazi ukwelapha. Wakhishwa esibhedlela esesimweni esizinzile ngoSepthemba 15, 2025, kanye nezincomo zokuqapha okuqhubekayo, okuhlanganisa izimpawu zesimila, ukusebenza kwesibindi, kanye nokuskena kwe-PET-CT. Indlela eqondiwe yalolu hlobo lokwelapha yanciphisa ubuthi besistimu ngenkathi ibhekana nendawo yesibindi yesimila.