ʻO nā pūnaewele TAEST16001 he mau pūnaewele T autologous i hana ʻia ma ke ʻano genetic e hōʻike ana i ka receptor T-cell NY-ESO-1-specific kiʻekiʻe (TCR) e kuhikuhi ana iā NY-ESO-1 (i hōʻike ʻia ma nā ʻano tumors like ʻole) positive soft tissue sarcoma (STS) i loko o ka pōʻaiapili o HLA-A * 02:01.
Ua hōʻike ʻia kahi haʻawina pae I o nā maʻi me STS holomua (NCT04318964) i ka palekana a me ka hōʻailona mua o ka pono ma ASCO 2022. He haʻawina hāmama kēia, lima hoʻokahi, hoʻonui ʻia ka lāʻau a me ka hoʻonui ʻana e loiloi i ka palekana, ka hoʻomanawanui, PK, PD a me ka pono mua o nā pūnaewele TAEST16001 i nā maʻi me ka sarcoma palupalu.
Nā Hualoaʻa: Ma ka lā 31 o Dekemaba 2021, ua kākau inoa ʻia he 12 mau maʻi me ka sarcoma palupalu holomua (M:F 7:5; awelika makahiki = 37.9; waena o nā regimen mua = 2 (pae 1-3)). Ua ʻae maikaʻi ʻia nā pūnaewele TAEST16001 me ka ʻole o ka palena o ka lāʻau. ʻO nā hanana ʻino papa ³ 3 i hōʻike pinepine ʻia ʻo lymphopenia (n = 12), leukopenia (n = 10), neutropenia (n = 11), anemia (n = 4), thrombocytopenia (n = 1), hypokalemia (n = 1), a me ke kuni (n = 1). ʻElua mau maʻi i hōʻike ʻia me ka cytokine release syndrome (nā papa 2) a ua hoʻopau ʻia ma hope o ka mālama ʻana i nā hōʻailona. ʻAʻohe o nā maʻi i loaʻa ka neurotoxicity, a i ʻole nā hanana ʻino koʻikoʻi e pili ana i ka hoʻokomo ʻana o nā cell. ʻAʻole i hiki i ka nui o ka lāʻau i ʻae ʻia (MTD). Ua hōʻike ka hoʻohālike PK he 6.23 mau lā ma hope o ka hoʻokomo ʻana o nā cell i ka Tmax o TAEST16001, a ʻaʻohe pilina ma waena o ka pane lapaʻau a me Cmax/AUC0-28. Ma waena o 12 mau maʻi i hiki ke loiloi ʻia ka pono, he 5 mau maʻi i loaʻa ka pane hapa, he 5 mau maʻi i loaʻa ka maʻi paʻa, a he 2 mau maʻi i loaʻa ka maʻi holomua. ʻO ka helu pane holoʻokoʻa he 41.7%. ʻO ka manawa waena i kahi pane mua he 1.9 mahina (pae, 0.9 a 3.0), a ʻo ka lōʻihi waena o ka pane he 14.1 mahina (pae, 5.0 a 14.2).
ʻO ka mea nui, ʻo ka mea maʻi ʻo T06 (kāne 42 makahiki), ka mea i loaʻa i ʻelua mau laina lapaʻau ma mua a ua ʻike i ka papa 2 CRS ma hope o ka mālama ʻana iā TAEST16001, ua hōʻike ʻo ia i kahi pane hapa o nā ʻeha metastatic o ka lima o luna a me nā māmā he nui ma hope o 4 mau pule o ka hoʻokomo ʻana o ke kelepona, e mālama ana ma mua o 14 mau mahina ma hope o ka mālama ʻana. ʻOiai ua noho mau nā ʻeha metastatic o ka māmā i kahi pane hapa nui a hiki i ka wā o ka holomua, ua hana ʻia ka mea maʻi i ka ʻoki ʻoki ʻana i kahi ʻeha ma ka lima o luna. ʻO kekahi mea maʻi ʻē aʻe, ʻo T02 (kāne 27 makahiki), ka mea i loaʻa ka myxoid liposarcoma hou ma ka wāwae ʻākau ma hope o ka loaʻa ʻana o ʻelima mau ʻokiʻoki, ua hōʻike pū i kahi pane hapa a ua hoʻomau ma mua o 1 makahiki ma hope o ka mālama ʻana.
I ka makahiki 2024, ua hōʻike ka American Society of Clinical Oncology (ASCO)phaʻawina haʻawina IIA o ka TCR-T affinity kiʻekiʻe (TAEST16001) e kuhikuhi ana iā NY-ESO-1 i loko o ka sarcoma ʻiʻo palupalu (NCT05549921).
Nā Hana: He haʻawina lima hoʻokahi kēia i wehe ʻia me ka lepili e loiloi i ka pono a me ka palekana o nā pūnaewele TAEST16001 i nā poʻe maʻi me STS holomua (NCT05549921). Ua hana ʻia nā apheresis i nā poʻe maʻi i kākau inoa ʻia, ua hoʻonui ʻia ko lākou mau pūnaewele T i hoʻokaʻawale ʻia ma vitro ma hope o ka transduction me kahi vector lentiviral e hōʻike ana i ka affinity kiʻekiʻe NY-ESO-1 TCR. Ua loaʻa i nā poʻe maʻi ka chemotherapy lymphodepleting 3 lā (cyclophosphamide 15 mg/kg/lā a me fludarabine 20 mg/m2/lā). Ua lawelawe ʻia nā pūnaewele TAEST16001 ma 1.2 × 1010± 30% mau pūnaewele (i hoʻoholo ʻia ma o kā mākou ʻikepili pae I) a ua loaʻa pū iā lākou ka inikini IL-2 sc 14 lā. Ua hoʻonohonoho ʻia ka pono o ka pahuhopu (e like me RECIST 1.1) ma ka helu pane holoʻokoʻa (ORR) =25% no ka hui mua o 12 mau maʻi.
Nā Hualoaʻa: I Ianuali 2024, ua kākau inoa ʻia he 8 mau maʻi (M:F 4: 4; makahiki awelika: 40 mau makahiki; nā regimen mua waena: 3 (pae: 2-5)). Ua hōʻike nā cell TAEST16001 i kahi ʻano palekana hiki ke hoʻokele ʻia e kūlike me ke aʻo ʻana o ka pae I ma mua. ʻO nā hanana ʻino maʻamau (n>1) i hōʻike ʻia (G) 3 he lymphocytopenia (n=8), ka emi ʻana o ka helu WBC (n=7), neutropenia (n=6), ka hoʻokiʻekiʻe ʻana o γ-GT (n=3), hypokalemia (n=2). ʻEono mau maʻi i loaʻa i ka cytokine release syndrome (CRS) (G3: 1; G2: 1; G1: 4), a ua loaʻa pū kekahi mau maʻi 2 i ka G1 ICANS, i hoʻopau loa ʻia ma hope o ka mālama ʻana i nā hōʻailona. ʻO ka mea nui, ma hope o ʻelua mau loiloi tumor, ua hōʻoia ʻo 4 i ka pane hapa, he 3 ka maʻi paʻa, a he 1 ka maʻi holomua. ʻO ka ORR ma ka lā palena he 50%. ʻO ka manawa waena i ka pane mua ʻana he 1.1 mahina (1.1 a 2.2) a ʻo ka lōʻihi waena o ka pane ʻana he 5.0 mahina (1.5 a 8.8). Ke nānā ʻia nei ka hapa nui o nā maʻi. I ka hōʻuluʻulu ʻana i ka ʻikepili no ka mahele like ma ka ʻāpana pae I, ʻo ORR ma ka mahele o 1.2 × 1010he 54.5% (6/11).
I kēia manawa, nui nā hoʻokolohua lapaʻau o nā ʻenehana anti-cancer hou ma Kina e ʻimi nei i nā maʻi. I ke kūkākūkā ʻana i nā lāʻau lapaʻau a me nā ʻenehana hou, hiki iā ʻoe ke hoʻokaʻaʻike aku i ka Beijing South Region Oncology Hospital International Department.
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1.https://www.xphcn.com/xiangxue/index_33.aspx
2.https://ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.11502
3.https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(23)00261-6
4.https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.11548
Ka manawa hoʻouna: Dec-18-2024