Kwayoyin TAEST16001 ƙwayoyin T ne masu aiki da kansu waɗanda aka ƙera ta hanyar halitta waɗanda ke bayyana babban haɗin kai na NY-ESO-1-specific T-cell receptor (TCR) wanda ke nufin NY-ESO-1 (wanda aka bayyana a cikin nau'ikan ciwace-ciwacen) mai kyau na sarcoma mai laushi na nama (STS) a cikin mahallin HLA-A*02:01.
Wani bincike na mataki na farko a cikin marasa lafiya da ke fama da ciwon daji mai tsanani (NCT04318964) ya nuna aminci da kuma alamar farko ta inganci a ASCO 2022. Wannan wani bincike ne da aka yi a hannu ɗaya, wanda aka yi shi da hannu ɗaya, wanda aka yi shi da kuma wanda aka yi amfani da shi wajen ƙara yawan ƙwayoyin cuta da kuma faɗaɗawa don tantance aminci, juriya, PK, PD da kuma ingancin farko na ƙwayoyin TAEST16001 a cikin marasa lafiya da ke fama da ciwon daji mai laushi.
Sakamako: Ya zuwa ranar 31 ga Disamba, 2021, an yi wa marasa lafiya 12 da ke fama da sarcoma mai laushi na nama (M:F 7:5; matsakaicin shekaru = 37.9; matsakaicin tsarin da aka riga aka yi = 2 (tsakanin 1-3)). Kwayoyin TAEST16001 sun sami juriya sosai ba tare da wani guba da ke iyakance allurai ba. Abubuwan da suka fi faruwa a matakin ³ 3 sune lymphopenia (n = 12), leukopenia (n = 10), neutropenia (n = 11), anemia (n = 4), thrombocytopenia (n = 1), hypokalemia (n = 1), da zazzabi (n = 1). Marasa lafiya biyu sun nuna alamun sakin cytokine (maki 2) kuma sun warke bayan an yi musu magani mai nuna alamun cutar. Babu ɗaya daga cikin marasa lafiyar da ke da cutar neurotoxicity, ko kuma mummunan sakamako masu alaƙa da jiko na ƙwayoyin halitta. Ba a kai matsakaicin adadin da aka yarda da shi ba (MTD). Tsarin PK ya nuna cewa Tmax na ƙwayoyin TAEST16001 sun kasance kwanaki 6.23 bayan an saka ƙwayoyin, kuma babu wata alaƙa tsakanin amsawar asibiti da Cmax/AUC0-28. Daga cikin marasa lafiya 12 da za a iya kimantawa da inganci, marasa lafiya 5 sun sami martani kaɗan, marasa lafiya 5 suna da rashin lafiya mai ɗorewa, kuma marasa lafiya 2 suna da ciwon da ke ci gaba da yaduwa. Jimillar amsawar shine 41.7%. Matsakaicin lokacin amsawar farko shine watanni 1.9 (tsakanin, 0.9 zuwa 3.0), kuma matsakaicin tsawon lokacin amsawar shine watanni 14.1 (tsakanin, 5.0 zuwa 14.2).
Abin lura shi ne, majiyyaci T06 (namiji mai shekaru 42), wanda ya taɓa samun magani sau biyu a baya kuma ya fuskanci CRS na mataki na 2 bayan maganin TAEST16001, ya nuna raunin hannu na sama da raunukan huhu da yawa bayan makonni 4 na jika ƙwayoyin halitta, yana riƙe da fiye da watanni 14 bayan magani. Ganin cewa raunukan huhu sun kasance babban martani ko da a lokacin ci gaba, an yi wa majiyyaci tiyata na wani rauni a hannun sama. Wani majiyyaci, T02 (namiji mai shekaru 27), wanda ya sake samun ciwon myxoid liposarcoma a ƙafar dama bayan an yi masa tiyata sau biyar, shi ma ya nuna raunin kuma ya ci gaba da fiye da shekara 1 bayan magani.
A shekarar 2024, ƙungiyar American Society of Clinical Oncology (ASCO) ta ba da rahoto game da raguwar yawan mace-mace a cikin jarirai.pNazarin IIA na TCR-T mai yawan alaƙa (TAEST16001) wanda ke nufin NY-ESO-1 a cikin sarcoma mai laushi na nama (NCT05549921).
Hanyoyi: Wannan wani bincike ne da aka buɗe, wanda aka yi wa alama da hannu ɗaya don tantance inganci da amincin ƙwayoyin TAEST16001 a cikin marasa lafiya da ke da STS mai ci gaba (NCT05549921). An yi wa marasa lafiya da aka yi wa rajista apheresis, ƙwayoyin T ɗinsu da aka keɓe sun faɗaɗa a cikin vitro bayan an yi musu transduction tare da vector lentiviral wanda ke nuna babban ƙarfin NY-ESO-1 TCR. Marasa lafiya sun karɓi maganin chemotherapy na kwana 3 na lymphodepleting (cyclophosphamide 15 mg/kg/rana da fludarabine 20 mg/m2/rana). An ba da ƙwayoyin TAEST16001 a 1.2 × 1010± 30% ƙwayoyin halitta (an ƙayyade su ta hanyar bayanan mataki na I) kuma sun karɓi allurar IL-2 sc na kwanaki 14. An saita ingancin da aka yi niyya (ga kowane RECIST 1.1) a jimlar ƙimar amsawa (ORR) = 25% ga rukunin marasa lafiya 12 na mataki na farko.
Sakamako: Ya zuwa watan Janairun 2024, an yi wa marasa lafiya 8 rajista (M:F 4: 4; matsakaicin shekaru: shekaru 40; matsakaicin tsarin da aka yi a baya: 3 (tsakanin: 2-5)). Kwayoyin TAEST16001 sun nuna yanayin aminci mai sarrafawa daidai da binciken mataki na farko na baya. Abubuwan da suka faru marasa kyau guda 3 (n>1) da aka ruwaito a matsayin sakamako (G) sune lymphocytopenia (n=8), raguwar adadin WBC (n=7), neutropenia (n=6), ƙaruwar γ-GT (n=3), hypokalemia (n=2). Marasa lafiya shida suna da cutar sakin cytokine (CRS) (G3: 1; G2: 1; G1: 4), kuma marasa lafiya 2 suma sun fuskanci G1 ICANS, duk sun warke gaba ɗaya bayan maganin alamun. Abu mafi mahimmanci, bayan aƙalla kimantawa guda biyu na ƙari, 4 sun tabbatar da wani ɓangare na amsawa, 3 suna da rashin lafiya mai ƙarfi, kuma 1 yana da cutar ci gaba. ORR a ranar ƙarshe shine 50%. Matsakaicin lokacin amsawar farko shine watanni 1.1 (1.1 zuwa 2.2) kuma matsakaicin tsawon lokacin amsawa shine watanni 5.0 (1.5 zuwa 8.8). Yawancin marasa lafiya har yanzu ana ci gaba da bin diddigin su. Lokacin da ake tattara bayanai game da wannan allurar a cikin kashi na farko, ORR a kashi na 1.2 × 1010ya kasance kashi 54.5% (6/11).
A halin yanzu, har yanzu akwai gwaje-gwaje da yawa na asibiti na sabbin fasahohin yaƙi da cutar kansa a China waɗanda ke neman marasa lafiya. Tuntuɓi kan sabbin magunguna da fasahohi, zaku iya tuntuɓar Sashen Ƙasa da Ƙasa na Asibitin Oncology na Yankin Kudu na Beijing.
Lambar Waya: 4008803716
Email：myimmnet@163.com
NAZARI
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
Lokacin Saƙo: Disamba-18-2024