Ke Kaua Nei i ka Hepatocellular Carcinoma me ka Bioocus GPC3 CAR-T Therapy

Ka Moʻolelo o ka Mea Maʻi

ʻO Pawan, he kanaka hoʻolaʻa mai India mai, ua ʻike ʻia he maʻi akepaʻa mau loa i hoʻopilikia ʻia e ka multifocal hepatocellular carcinoma (HCC) i ʻAukake 2024. I kona mau makahiki he 67 i ka wā i ʻike ʻia ai (e 68 ona makahiki i ka wā o ka mālama ʻana), ua kū ʻo ia i kahi maʻi ʻino me nā ʻeha akepaʻa he nui, nā māka tumor kiʻekiʻe e like me AFP a me PIVKA-II, anemia, nā ʻano enzyme ate, a me nā metastases iwi ma hope. ʻOiai ke hana nei ʻo ia i ka transarterial radioembolization (TARE), transarterial chemoembolization (TACE), immunotherapy (Atezolizumab + Bevacizumab, Tremelimumab + Durvalumab), a me nā therapies i kuhikuhi ʻia (Lenvatinib, Cabozantinib, Regorafenib), ua holomua kona maʻi. Ua hōʻike ka hoʻāʻo genetic i nā mutations ma TP53, KRAS, CDKN2A, CTNNB1, a me ARID1A, me ka haʻahaʻa o ka hōʻike ʻana o PD-L1 a me ka HRD negativity, e hōʻike ana i ka pane palena i kekahi mau mea hoʻopaʻa. I ka ʻimi ʻana i nā hoʻonā holomua, ua kuhikuhi ʻia ʻo Pawan i ka Halemai Kanesa ʻo Tianjin ma o Bioocus no kā mākou lāʻau lapaʻau GPC3 CAR-T autologous ma lalo o ka helu lapaʻau P1544.

Ka Huakaʻi Lapaʻau

Ua hoʻomaka ka mālama ʻana o Pawan iā CAR-T me ka leukapheresis ma ʻAukake 11, 2025, a ukali ʻia e ka hana ʻana a me ka hoʻokomo ʻana ma Kepakemapa 2, 2025. Ua loaʻa iā ia kahi mahele o 4.73 × 10^8 mau cell CAR-T, e kuhikuhi ana iā GPC3, kahi māka i hoʻonui nui ʻia ma HCC. ʻO ka hoʻomaʻamaʻa mua ʻana o ka hoʻokomo ʻana me ka fludarabine a me ka cyclophosphamide e hoʻoikaika i ka engraftment. Ma hope o ka hoʻokomo ʻana, ua nānā ʻia kona koko peripheral no ka hoʻonui ʻana o CAR-T i nā lā 4 (D4), 7 (D7), 10 (D10), a me 12 (D12).

• D4 (Kepakemapa 6, 2025):Nā pūnaewele CAR-T ma 5.15% o nā pūnaewele CD3+ T (waiwai paʻa: 9.27 × 10^6/L), e hōʻike ana i ka hoʻopili mua ʻana.
• D7 (Kepakemapa 9, 2025):Ua piʻi i ka 3.97% (6.12 × 10^7/L), e hōʻike ana i ka hoʻonui ʻana.
• D10 (Kepakemapa 12, 2025):04% (9.07 × 10^6/L).
• D12 (Kepakemapa 14, 2025):Paʻa ma 2.82% (2.26 × 10^7/L), me ka huina o nā pūnaewele T ma 5.4 × 10^9/L, CD3+ ma 14.87%, nā pūnaewele T cytotoxic CD8+ i hoʻokiʻekiʻe ʻia ma 77.88%, a me nā hui CAR-T kaulike (e laʻa, 2.46% CD8+CARGPC3+/CD8+).

I ka wā o ka mālama ʻia ʻana ma ka haukapila mai ʻAukake 11 a i Kepakemapa 15, 2025, ua ʻike ʻo Pawan i nā hopena ʻaoʻao iki, me ke kuni haʻahaʻa (a hiki i ka 38.5°C), ka luhi, a me ka piʻi ʻana o ka enzyme ate, i mālama ʻia me ke kākoʻo me ka ʻole o ka cytokine release syndrome koʻikoʻi (CRS grade 1) a i ʻole ka neurotoxicity. Ua noho paʻa nā hōʻailona koʻikoʻi, a ʻo ka mālama kākoʻo e komo pū ana me nā lāʻau anti-infectious, ka meaʻai, a me ka nānā ʻana i nā pilikia e like me ka ascites.

Nā Hopena Koʻikoʻi

ʻOiai he haʻahaʻa ka hoʻonui ʻana o CAR-T, ua hōʻike ʻo ia i ka hoʻomau a me ka hana anti-tumor, e pili ana me nā māka tumor i hoʻopaʻa ʻia a ʻaʻohe holomua koke ma ke kiʻi hahai. Ua kūlike ka hihia o Pawan me ka holomua o Bioocus ma GPC3 CAR-T no HCC, kahi hiki i ka hoʻomau haʻahaʻa ke alakaʻi i nā pane paʻa i nā poʻe maʻi paʻakikī. Ua hoʻokuʻu ʻia ʻo ia ma ke kūlana paʻa ma Kepakemapa 15, 2025, me nā ʻōlelo aʻoaʻo no ka nānā mau ʻana, me nā māka tumor, ka hana ate, a me nā scan PET-CT. Ua hoʻemi ke ʻano o kēia lāʻau lapaʻau i ka ʻawahia systemic i ka wā e hoʻoponopono ana i ke kaiapuni ate o ka tumor.