Ho Loantša Kankere ea Hepatocellular ka Kalafo ea Bioocus GPC3 CAR-T

Semelo sa Mokuli

Pawan, motho ea inehetseng oa India, o ile a fumanoa a e-na le lefu la sebete le sa foleng le rarahaneng ke multifocal hepatocellular carcinoma (HCC) ka Phato 2024. Ha a le lilemo li 67 ha a fumanoa (a le lilemo li 68 nakong ea kalafo), o ile a tobana le lefu le matla le nang le liso tse ngata tsa sebete, matšoao a phahameng a hlahala joalo ka AFP le PIVKA-II, khaello ea mali, mathata a enzyme ea sebete, le metastases ea masapo hamorao. Leha a ile a etsoa transarterial radioembolization (TARE), transarterial chemoembolization (TACE), immunotherapy (Atezolizumab + Bevacizumab, Tremelimumab + Durvalumab), le mekhoa ea phekolo e reretsoeng (Lenvatinib, Cabozantinib, Regorafenib), lefu la hae le ile la tsoela pele. Liteko tsa liphatsa tsa lefutso li senotse liphetoho ho TP53, KRAS, CDKN2A, CTNNB1, le ARID1A, ka polelo e tlase ea PD-L1 le ho se nepahale ha HRD, ho bontšang karabelo e fokolang ho lithibela-mafu tse itseng. Ha a batla ditharollo tse tswetseng pele, Pawan o ile a romelwa Sepetleleng sa Kankere sa Tianjin ka Bioocus bakeng sa kalafo ya rona ya autologous GPC3 CAR-T tlasa nomoro ya kalafo P1544.

Leeto la Kalafo

Kalafo ea Pawan ea CAR-T e qalile ka leukapheresis ka la 11 Phato, 2025, ea lateloa ke tlhahiso le infusion ka la 2 Loetse, 2025. O ile a fuoa tekanyo ea lisele tsa CAR-T tsa 4.73 × 10^8, tse shebaneng le GPC3, letšoao le hlahisitsoeng haholo ho HCC. Mokhoa oa pele oa infusion o ne o kenyelletsa fludarabine le cyclophosphamide ho ntlafatsa ho kenngoa ha mali. Kamora ho kenngoa, mali a hae a ka ntle a ile a beoa leihlo bakeng sa katoloso ea CAR-T Matsatsing a 4 (D4), 7 (D7), 10 (D10), le 12 (D12).

• D4 (Loetse 6, 2025):Lisele tsa CAR-T ho 5.15% ea lisele tsa CD3+ T (boleng bo felletseng: 9.27 × 10^6/L), e leng se bontšang ho kenngoa ha lisele qalong.
• D7 (Loetse 9, 2025):E fihlile sehlohlolong ho 3.97% (6.12 × 10^7/L), e bonts'a keketseho e mafolofolo.
• D10 (La 12 Loetse, 2025):04% (9.07 × 10^6/L).
• D12 (La 14 Loetse, 2025):E tsitsitse ho 2.82% (2.26 × 10^7/L), ka lisele tsohle tsa T ho 5.4 × 10^9/L, CD3+ ho 14.87%, lisele tse phahameng tsa T tse nang le chefo ea CD8+ ho 77.88%, le likaroloana tse leka-lekaneng tsa CAR-T (mohlala, 2.46% CD8+CARGPC3+/CD8+).

Nakong ea ho kena sepetlele ho tloha ka la 11 Phato ho isa la 15 Loetse, 2025, Pawan o bile le litla-morao tse bobebe, ho kenyeletsoa le feberu ea maemo a tlase (ho fihlela ho 38.5°C), mokhathala, le keketseho ea li-enzyme tsa sebete tse sa feleng, tse ileng tsa laoloa ka tšehetso ntle le lefu le matla la ho lokolloa ha cytokine (CRS grade 1) kapa chefo ea methapo ea kutlo. Matšoao a bohlokoa a ile a lula a tsitsitse, 'me tlhokomelo e tšehetsang e ne e kenyelletsa lithibela-mafu, phepo e nepahetseng le ho beha leihlo mathata a kang ascites.

Liphetho tse Ikhethang

Katoloso ea CAR-T, leha e le nyane, e bontšitse ho phehella le ts'ebetso ea ho loantša hlahala, e amanang le matšoao a hlahala a tsitsitseng 'me ha ho na tsoelo-pele e potlakileng litšoantšong tse latelang. Nyeoe ea Pawan e tsamaisana le katleho ea Bioocus ho GPC3 CAR-T bakeng sa HCC, moo esita le ho phehella ho tlase ho ka lebisang likarabelong tse tšoarellang ho bakuli ba sa laoleheng. O ile a lokolloa a le boemong bo tsitsitseng ka la 15 Loetse, 2025, ka likhothaletso tsa tlhokomelo e tsoelang pele, ho kenyeletsoa matšoao a hlahala, ts'ebetso ea sebete le li-scan tsa PET-CT. Mokhoa ona o reretsoeng kalafo o fokolitse chefo ea 'mele ha o ntse o sebetsana le tikoloho ea sebete ea hlahala.