Kulimbana ndi Khansa ya Hepatocellular ndi Bioocus GPC3 CAR-T Therapy

Mbiri ya Odwala

Pawan, munthu wodzipereka wochokera ku India, adapezeka ndi matenda osatha a chiwindi omwe amakumana ndi multifocal hepatocellular carcinoma (HCC) mu Ogasiti 2024. Ali ndi zaka 67 atapezeka ndi matendawa (atakwanitsa zaka 68 panthawi ya chithandizo), adakumana ndi matenda oopsa okhala ndi zilonda zingapo za chiwindi, zizindikiro zazikulu za chotupa monga AFP ndi PIVKA-II, kuchepa kwa magazi m'thupi, zolakwika za enzyme ya chiwindi, komanso kufalikira kwa mafupa pambuyo pake. Ngakhale adakumana ndi transarterial radioembolization (TARE), transarterial chemoembolization (TACE), immunotherapy (Atezolizumab + Bevacizumab, Tremelimumab + Durvalumab), ndi mankhwala ochizira (Lenvatinib, Cabozantinib, Regorafenib), matenda ake adapita patsogolo. Kuyesa majini kudawonetsa kusintha kwa TP53, KRAS, CDKN2A, CTNNB1, ndi ARID1A, ndi mawonekedwe otsika a PD-L1 ndi HRD negativity, zomwe zikusonyeza kuyankha kochepa kwa zoletsa zina. Pofuna kupeza njira zamakono, Pawan adatumizidwa ku Chipatala cha Tianjin Cancer kudzera mu Bioocus kuti akalandire chithandizo chathu cha autologous GPC3 CAR-T pansi pa nambala P1544.

Ulendo wa Chithandizo

Chithandizo cha Pawan cha CAR-T chinayamba ndi leukapheresis pa Ogasiti 11, 2025, kutsatiridwa ndi kupanga ndi kulowetsedwa pa Seputembala 2, 2025. Analandira mlingo wa maselo a CAR-T a 4.73 × 10^8, akuyang'ana GPC3, chizindikiro chomwe chinaperekedwa mopitirira muyeso mu HCC. Kukonza kwa mankhwala asanayambe kulowetsedwa kunaphatikizapo fludarabine ndi cyclophosphamide kuti awonjezere kulowetsedwa. Pambuyo polowetsedwa, magazi ake am'mbali mwa thupi adayang'aniridwa kuti aone kukula kwa CAR-T pa Masiku 4 (D4), 7 (D7), 10 (D10), ndi 12 (D12).

• D4 (Seputembala 6, 2025):Maselo a CAR-T pa 5.15% ya maselo a CD3+ T (mtengo wake wonse ndi 9.27 × 10^6/L), zomwe zikusonyeza kulowetsedwa koyamba.
• D7 (Seputembala 9, 2025):Inafika pachimake pa 3.97% (6.12 × 10^7/L), kusonyeza kuchulukana kwamphamvu.
• D10 (Seputembala 12, 2025):04% (9.07 × 10^6/L).
• D12 (Seputembala 14, 2025):Yokhazikika pa 2.82% (2.26 × 10^7/L), ndi maselo onse a T pa 5.4 × 10^9/L, CD3+ pa 14.87%, maselo a T a cytotoxic a CD8+ okwera pa 77.88%, ndi ma CAR-T subsets oyenerera (monga, 2.46% CD8+CARGPC3+/CD8+).

Pa nthawi yomwe anali m'chipatala kuyambira pa Ogasiti 11 mpaka Seputembala 15, 2025, Pawan adakumana ndi zotsatirapo zoyipa pang'ono, kuphatikizapo kutentha thupi pang'ono (mpaka 38.5°C), kutopa, ndi kukwera kwa ma enzyme a chiwindi kwakanthawi, zomwe zidathandizidwa popanda cytokine release syndrome (CRS grade 1) kapena neurotoxicity. Zizindikiro zofunika kwambiri zidakhazikika, ndipo chisamaliro chothandizira chidaphatikizapo mankhwala oletsa matenda, zakudya, ndi kuyang'anira zovuta monga ascites.

Zotsatira Zabwino Kwambiri

Kukula kwa CAR-T, ngakhale kuti kunali kochepa, kunasonyeza kupirira ndi ntchito yolimbana ndi chotupa, zomwe zikugwirizana ndi zizindikiro zokhazikika za chotupa ndipo palibe kupita patsogolo mwachangu pa kujambula zithunzi zotsatizana. Nkhani ya Pawan ikugwirizana ndi kupambana kwa Bioocus mu GPC3 CAR-T ya HCC, komwe ngakhale kupirira kochepa kungayambitse mayankho olimba mwa odwala omwe safuna chithandizo. Anatulutsidwa ali bwino pa Seputembala 15, 2025, ndi malangizo oti aziyang'aniridwa nthawi zonse, kuphatikizapo zizindikiro za chotupa, ntchito ya chiwindi, ndi PET-CT scans. Njira yochizira iyi inachepetsa poizoni m'thupi pamene ikuthana ndi vuto la chiwindi cha chotupacho.