Te Pakanga ki te Mate Pukupuku Ā-pūtau me te Whakaora Bioocus GPC3 CAR-T

Papamuri o te Tūroro

I te marama o Ākuhata 2024, i kitea he mate ate mau tonu nā te mate pukupuku hepatocellular maha-focal (HCC) a Pawan. I te 67 o ōna tau i te wā i kitea ai te mate (i te 68 o ōna tau i te wā e rongoatia ana), i pāngia ia e te mate kino me ngā whara ate maha, ngā tohu pukupuku teitei pērā i te AFP me te PIVKA-II, te anemia, ngā rerekētanga o te whākōkī ate, me ngā metastases wheua i muri mai. Ahakoa te whai i te transarterial radioembolization (TARE), te transarterial chemoembolization (TACE), te immunotherapy (Atezolizumab + Bevacizumab, Tremelimumab + Durvalumab), me ngā maimoatanga kua tohua (Lenvatinib, Cabozantinib, Regorafenib), i haere tonu tana mate. I whakaatuhia e ngā whakamātautau ira ngā whakarerekētanga ira i roto i te TP53, KRAS, CDKN2A, CTNNB1, me te ARID1A, me te iti o te whakaaturanga PD-L1 me te kino o te HRD, e tohu ana i te iti o te urupare ki ētahi aukati. I a ia e rapu ana i ngā otinga matatau, i tukuna a Pawan ki te Hōhipera Matepukupuku o Tianjin mā Bioocus mō tā mātou rongoā GPC3 CAR-T aunoa i raro i te nama maimoatanga P1544.

Te Haerenga Maimoatanga

I tīmata te maimoatanga CAR-T a Pawan mā te leukapheresis i te 11 o Ākuhata, 2025, ā, i muri mai ko te hanga me te werohanga i te 2 o Hepetema, 2025. I whiwhi ia i te horopeta o te 4.73 × 10^8 pūtau CAR-T, e aro ana ki a GPC3, he tohu i nui rawa te whakaputanga i roto i te HCC. Ko te whakatikatika i mua i te werohanga i whakaurua ko te fludarabine me te cyclophosphamide hei whakarei ake i te engraftment. I muri i te werohanga, i tirotirohia ōna toto ā-taha mō te whānui o te CAR-T i ngā Rā 4 (D4), 7 (D7), 10 (D10), me te 12 (D12).

• D4 (6 o Hepetema, 2025):Ngā pūtau CAR-T i te 5.15% o ngā pūtau CD3+ T (uara tino: 9.27 × 10^6/L), e tohu ana i te whakaurunga tuatahi.
• D7 (9 o Hepetema, 2025):I eke ki te 3.97% (6.12 × 10^7/L), e whakaatu ana i te tipu kaha.
• D10 (12 o Hepetema, 2025):04% (9.07 × 10^6/L).
• D12 (14 o Hepetema, 2025):I whakapūmautia ki te 2.82% (2.26 × 10^7/L), me te tapeke o ngā pūtau-T ki te 5.4 × 10^9/L, CD3+ ki te 14.87%, ngā pūtau-T paitini CD8+ kua piki ake ki te 77.88%, me ngā huinga iti CAR-T kua taurite (hei tauira, 2.46% CD8+CARGPC3+/CD8+).

I te wā i noho hōhipera ai a Pawan mai i te 11 o Ākuhata ki te 15 o Hepetema, 2025, i pāngia ia e ngā pānga taha ngawari, tae atu ki te kirika iti (tae atu ki te 38.5°C), te ngenge, me te pikinga poto o ngā whākōkī ate, i whakahaeretia me te tautoko me te kore he mate tukunga cytokine nui (CRS grade 1) he paitini roro rānei. I noho pumau tonu ngā tohu ora, ā, ko te tiaki tautoko i uru atu ki ngā rongoā ārai mate, te kai totika, me te aroturuki mō ngā raruraru pēnei i te ascites.

Ngā Hua Tino Pai

Ahakoa he iti noa te whānui o te CAR-T, i whakaatu i te pumau me te mahi ārai-puku, e hono ana ki ngā tohu pukupuku kua pumau, ā, kāore he whanaketanga tonu i runga i te whakaahua whai muri. E hangai ana te take a Pawan ki te angitu o Bioocus i roto i te GPC3 CAR-T mō te HCC, ahakoa te pumau iti ka taea te arahi ki ngā urupare roa i roto i ngā tūroro uaua. I tukuna ia i roto i te āhua pumau i te 15 o Hepetema, 2025, me ngā taunakitanga mō te aroturuki tonu, tae atu ki ngā tohu pukupuku, te mahi ate, me ngā matawai PET-CT. Ko te huarahi arotahi o tēnei rongoā i whakaiti i te paitini pūnaha i te wā e aro ana ki te taiao ate o te pukupuku.