Kurwisa Hepatocellular Carcinoma neBioocus GPC3 CAR-T Therapy

Nhoroondo yeMurwere

Pawan, munhu akazvipira kubva kuIndia, akaonekwa aine chirwere chechiropa chisingaperi chakakonzerwa ne multifocal hepatocellular carcinoma (HCC) muna Nyamavhuvhu 2024. Ava nemakore 67 ekuberekwa paakaonekwa kuti ane chirwere ichi (ava nemakore 68 ekuberekwa panguva yekurapwa), akasangana nechirwere chakasimba chine maronda akawanda echiropa, zviratidzo zvegomarara zvakaita seAFP nePIVKA-II, anemia, kusashanda zvakanaka kwema enzyme echiropa, uye kupararira kwemapfupa mushure mekufa. Kunyangwe akaongororwa ne transarterial radioembolization (TARE), transarterial chemoembolization (TACE), immunotherapy (Atezolizumab + Bevacizumab, Tremelimumab + Durvalumab), uye mishonga yakanangwa (Lenvatinib, Cabozantinib, Regorafenib), chirwere chake chakaenderera mberi. Kuongororwa kwemajini kwakaratidza shanduko muTP53, KRAS, CDKN2A, CTNNB1, uye ARID1A, nekutaura kwakaderera kwePD-L1 uye HRD negativity, zvichiratidza kusapindura kwakakwana kune zvimwe zvinodzivisa. Achitsvaga mhinduro dzemhando yepamusoro, Pawan akatumirwa kuTianjin Cancer Hospital kuburikidza neBioocus kuti apihwe autologous GPC3 CAR-T therapy pasi penhamba P1544.

Rwendo rweKurapwa

Kurapwa kwaPawan kweCAR-T kwakatanga ne leukapheresis musi wa11 Nyamavhuvhu, 2025, kuchiteverwa nekugadzirwa uye kuiswa mushonga musi wa2 Gunyana, 2025. Akapihwa mushonga we4.73 × 10^8 CAR-T cells, achinanga kuGPC3, chiratidzo chakanyanya kuratidzwa muHCC. Kugadziriswa kwemushonga usati waiswa mushonga kwaisanganisira fludarabine necyclophosphamide kuti zviwedzere kupinza ropa mumuviri. Mushure mekuiswa mushonga, ropa rake repanze rakatariswa kuti CAR-T yakawedzera sei paMazuva 4 (D4), 7 (D7), 10 (D10), uye 12 (D12).

• D4 (Gunyana 6, 2025):Masero eCAR-T ari pa5.15% yemasero eCD3+ T (kukosha kwakakwana: 9.27 × 10^6/L), zvichiratidza kuiswa kwekutanga.
• D7 (Gunyana 9, 2025):Yakasvika pa3.97% (6.12 × 10^7/L), ichiratidza kuwanda kwayo.
• D10 (Gunyana 12, 2025):04% (9.07 × 10^6/L).
• D12 (Gunyana 14, 2025):Yakagadzikana pa2.82% (2.26 × 10^7/L), ine masero ese eT pa5.4 × 10^9/L, CD3+ pa14.87%, masero eT ane chepfu akakwira eCD8+ pa77.88%, uye CAR-T subsets dzakaringana (semuenzaniso, 2.46% CD8+CARGPC3+/CD8+).

Munguva yekurara muchipatara kubva musi wa11 Nyamavhuvhu kusvika 15 Gunyana, 2025, Pawan akasangana nemigumisiro isina kunaka, kusanganisira fivha yakaderera (kusvika 38.5°C), kuneta, uye kuwedzerwa kwema enzyme echiropa kwenguva pfupi, zvakarapwa nerutsigiro pasina cytokine release syndrome (CRS grade 1) kana neurotoxicity. Zviratidzo zvakakosha zvakaramba zvakagadzikana, uye rubatsiro rwekutsigira rwaisanganisira mishonga inorwisa utachiona, kudya kunovaka muviri, uye kutarisa matambudziko akaita seascites.

Migumisiro Yakanaka

Kuwedzera kweCAR-T, kunyangwe kuri kushoma, kwakaratidza kuramba kuripo uye kushanda kwekudzivirira bundu, zvichienderana nezviratidzo zvebundu zvakagadzikana uye pasina kufambira mberi nekukurumidza pamifananidzo yekutevera. Nyaya yaPawan inoenderana nekubudirira kwaBioocus muGPC3 CAR-T yeHCC, uko kunyangwe kuramba kuripo zvishoma kunogona kutungamira kumhinduro dzinogara kwenguva refu kune varwere vasingachadi kurapwa. Akaburitswa ari mumamiriro ezvinhu akagadzikana musi waGunyana 15, 2025, pamwe nemazano ekutarisa nguva dzose, kusanganisira zviratidzo zvebundu, mashandiro echiropa, uye PET-CT scans. Nzira iyi yekurapa yakaderedza chepfu mumuviri uku ichigadzirisa mamiriro echiropa ebundu.