Ukulwa neHepatocellular Carcinoma ngeBioocus GPC3 CAR-T Therapy

Imvelaphi yesigulane

UPawan, umntu ozinikeleyo waseIndiya, wafunyaniswa enesifo sesibindi esinganyangekiyo esiyinkimbinkimbi yi-multifocal hepatocellular carcinoma (HCC) ngo-Agasti 2024. Xa wayeneminyaka engama-67 ubudala ekuxilongweni kwakhe (egqiba iminyaka engama-68 ngexesha lonyango), wajongana nesifo esibi esinezilonda ezininzi zesibindi, iimpawu ze-tumor eziphezulu ezifana ne-AFP kunye ne-PIVKA-II, i-anemia, iingxaki ze-enzyme yesibindi, kunye ne-metastases yamathambo kamva. Nangona wayesebenzisa i-transarterial radioembolization (TARE), i-transarterial chemoembolization (TACE), i-immunotherapy (Atezolizumab + Bevacizumab, Tremelimumab + Durvalumab), kunye nonyango olujoliswe kulo (Lenvatinib, Cabozantinib, Regorafenib), isifo sakhe saqhubeka. Uvavanyo lwe-genetic lubonise utshintsho kwi-TP53, KRAS, CDKN2A, CTNNB1, kunye ne-ARID1A, kunye nokubonakaliswa okuphantsi kwe-PD-L1 kunye nokungakhathali kwe-HRD, okubonisa impendulo encinci kwii-inhibitors ezithile. Efuna izisombululo eziphambili, uPawan wathunyelwa kwiSibhedlele soMhlaza saseTianjin ngeBioocus ukuze afumane unyango lwethu lwe-autologous GPC3 CAR-T phantsi konyango oluyinombolo P1544.

Uhambo Lonyango

Unyango lukaPawan lwe-CAR-T lwaqala nge-leukapheresis nge-11 ka-Agasti 2025, kwalandela ukwenziwa kunye nokufakwa ngoSeptemba 2, 2025. Wafumana idosi yeeseli ze-CAR-T eziyi-4.73 × 10^8, ejolise kwi-GPC3, uphawu olugqithisileyo kwi-HCC. Ukulungiswa kwe-pre-infusion kwakubandakanya i-fludarabine kunye ne-cyclophosphamide ukuphucula i-engraftment. Emva kokufakwa, igazi lakhe elingaphandle lalijongwa ukuba linwenwe yi-CAR-T kwiintsuku zesi-4 (D4), 7 (D7), 10 (D10), kunye ne-12 (D12).

• D4 (nge-6 kaSeptemba, 2025):Iiseli ze-CAR-T kwi-5.15% yeeseli ze-CD3+ T (ixabiso elipheleleyo: 9.27 × 10^6/L), nto leyo ebonisa ukufakwa kokuqala.
• D7 (nge-9 kaSeptemba, 2025):Ifikelele kwi-3.97% (6.12 × 10^7/L), ibonisa ukwanda okusebenzayo.
• D10 (nge-12 kaSeptemba, 2025):04% (9.07 × 10^6/L).
• D12 (nge-14 kaSeptemba, 2025):Izinzile kwi-2.82% (2.26 × 10^7/L), kunye nee-T cells zizonke kwi-5.4 × 10^9/L, i-CD3+ kwi-14.87%, ii-T cells ze-cytotoxic ze-CD8+ eziphezulu kwi-77.88%, kunye nee-CAR-T subsets ezilinganisiweyo (umz., 2.46% CD8+CARGPC3+/CD8+).

Ngexesha lokulaliswa esibhedlele ukususela nge-11 ka-Agasti ukuya kwi-15 kaSeptemba, ngo-2025, uPawan wafumana iziphumo ebezingalindelekanga ezingephi, kuquka umkhuhlane ophantsi (ukuya kuthi ga kwi-38.5°C), ukudinwa, kunye nokunyuka kwe-enzyme yesibindi okwethutyana, okulawulwa ngoncedo ngaphandle kwe-cytokine release syndrome enzima (i-CRS grade 1) okanye ubuthi be-neurotoxicity. Iimpawu ezibalulekileyo zahlala zizinzile, kwaye ukhathalelo oluxhasayo lwaluquka ukulwa nosulelo, ukutya okunesondlo, kunye nokubeka esweni iingxaki ezifana ne-ascites.

Iziphumo Ezibalaseleyo

Ukwandiswa kwe-CAR-T, nangona kuncinci, kubonise ukuqina nokusebenza kokulwa nethumba, kuhambelana neempawu zethumba ezizinzileyo kwaye akukho nkqubela phambili kwangoko kwimifanekiso yokulandelela. Ityala likaPawan lihambelana nempumelelo yeBioocus kwi-GPC3 CAR-T ye-HCC, apho nokuqina okuphantsi kunokukhokelela kwiimpendulo ezihlala ixesha elide kwizigulana ezingafuni nyango. Wakhutshwa ekwimeko ezinzileyo ngoSeptemba 15, 2025, kunye neengcebiso zokujonga ngokuqhubekayo, kubandakanya iimpawu zethumba, ukusebenza kwesibindi, kunye ne-PET-CT scans. Le ndlela ijoliswe kuyo yonyango yanciphisa ubuthi benkqubo yomzimba ngelixa ijongana nendawo yesibindi yethumba.