Amaseli e-TAEST16001 angamaseli e-T akhiwe ngofuzo aveza i-NY-ESO-1-specific T-cell receptor (TCR) egxile ku-NY-ESO-1 (evezwa ezinhlakeni eziningi) i-positive soft tissue sarcoma (STS) kumongo we-HLA-A*02:01.
Ucwaningo lwesigaba sokuqala ezigulini ezine-STS ethuthukisiwe (NCT04318964) lubonise ukuphepha kanye nesibonakaliso sokuqala sokusebenza kahle ku-ASCO 2022. Lolu ucwaningo oluvulekile, olungalodwa, lokwenyuka komthamo kanye nokwandiswa ukuze kuhlolwe ukuphepha, ukubekezeleleka, i-PK, i-PD kanye nokusebenza kokuqala kwamaseli e-TAEST16001 ezigulini ezine-sarcoma yezicubu ezithambile.
Imiphumela: Kusukela ngomhlaka-31 Disemba 2021, iziguli ezingu-12 ezine-sarcoma yezicubu ezithambile ezithuthukisiwe zabhaliswa (M:F 7:5; ubudala obuphakathi = 37.9; izindlela zangaphambilini eziphakathi = 2 (ububanzi 1-3)). Amaseli e-TAEST16001 abekezelelwa kahle ngaphandle kokunciphisa ubuthi ngesilinganiso. Izehlakalo ezimbi ezibikwa kakhulu zebanga ³ 3 kwakuyi-lymphopenia (n = 12), i-leukopenia (n = 10), i-neutropenia (n = 11), i-anemia (n = 4), i-thrombocytopenia (n = 1), i-hypokalemia (n = 1), kanye nomkhuhlane (n = 1). Iziguli ezimbili zavezwa yi-cytokine release syndrome (amabanga 2) futhi zaphela ngemva kokwelashwa okunezimpawu. Akekho kuziguli owayenobuthi be-neurological, noma izehlakalo ezimbi kakhulu ezihlobene nokufakwa kweseli. Umthamo obekezelelwe ophezulu (MTD) awuzange ufinyelelwe. Ukumodela kwe-PK kubonise ukuthi i-Tmax yamaseli e-TAEST16001 yayizinsuku ezingu-6.23 ngemuva kokufakwa kwamaseli, futhi kwakungekho buhlobo phakathi kwempendulo yezokwelapha kanye ne-Cmax/AUC0-28. Phakathi kweziguli ezingu-12 ezihlolwa ngempumelelo, iziguli ezi-5 zazinempendulo engaphelele, iziguli ezi-5 zazinesifo esizinzile, kanti iziguli ezi-2 zazinesifo esiqhubekayo. Izinga lokuphendula lilonke lalingu-41.7%. Isikhathi esimaphakathi sempendulo yokuqala sasiyizinyanga ezingu-1.9 (ububanzi, 0.9 kuya ku-3.0), kanti isikhathi esimaphakathi sempendulo sasiyizinyanga ezingu-14.1 (ububanzi, 5.0 kuya ku-14.2).
Okuphawulekayo ukuthi isiguli u-T06 (owesilisa oneminyaka engu-42 ubudala), esasithole imigqa emibili yokwelashwa ngaphambilini futhi sathola i-CRS yebanga lesi-2 ngemuva kokwelashwa nge-TAEST16001, sabonisa impendulo engaphelele yezilonda zengalo engenhla kanye nezilonda eziningi zephaphu ezisakazekile ngemuva kwamasonto ama-4 okufakwa kweseli, sagcina izinyanga ezingaphezu kwe-14 ngemuva kokwelashwa. Njengoba izilonda zephaphu ezisakazekile zahlala ziyimpendulo enhle engaphelele ngisho nangesikhathi sokuqhubeka, isiguli sahlinzwa ngokuhlinzwa isilonda engalweni engenhla. Esinye isiguli, u-T02 (owesilisa oneminyaka engu-27 ubudala), owayene-myxoid liposarcoma ephindelelayo emlenzeni wesokudla ngemuva kokuhlinzwa okuhlanu, naye wabonisa impendulo engaphelele futhi wahlala isikhathi esingaphezu konyaka owodwa ngemuva kokwelashwa.
Ngo-2024, i-American Society of Clinical Oncology (ASCO) ibike ukuthipUcwaningo lwe-hase IIA lwe-high-affinity TCR-T (TAEST16001) oluqondiswe ku-NY-ESO-1 ku-sarcoma yezicubu ezithambile (NCT05549921).
Izindlela: Lolu ucwaningo oluvulekile, olunengalo eyodwa lokuhlola ukusebenza kahle kanye nokuphepha kwamaseli e-TAEST16001 ezigulini ezine-STS ethuthukile (NCT05549921). Iziguli ezibhalisiwe zenze i-apheresis, amaseli azo e-T ahlukanisiwe anda ngaphakathi kwe-vitro ngemuva kokudluliselwa nge-lentiviral vector eveza ukusondelana okuphezulu kwe-NY-ESO-1 TCR. Iziguli zithole i-chemotherapy ye-lymphodepleting yezinsuku ezi-3 (i-cyclophosphamide 15 mg/kg/ngosuku kanye ne-fludarabine 20 mg/m2/ngosuku). Amaseli e-TAEST16001 anikezwe ku-1.2 × 1010Amaseli angu-± 30% (anqunywa ngedatha yethu yesigaba I) futhi athole nomjovo we-IL-2 sc wezinsuku eziyi-14. Ukusebenza kahle komgomo (ngokwe-RECIST 1.1) kwabekwa kuzinga lokuphendula eliphelele (ORR) = 25% eqenjini lesigaba sokuqala leziguli ezingu-12.
Imiphumela: Kusukela ngoJanuwari 2024, iziguli ezingu-8 zabhaliswa (M:F 4:4; iminyaka emaphakathi: iminyaka engu-40; izindlela zokwelapha zangaphambilini ezimaphakathi: 3 (ububanzi:2-5)). Amaseli e-TAEST16001 abonise iphrofayili yokuphepha elawulekayo ehambisana nesifundo sangaphambilini sesigaba soku-1. Izehlakalo ezimbi ezivamile (n>1) ezibikiwe zebanga (G) 3 kwakuyi-lymphocytopenia (n=8), ukwehla kwenani le-WBC (n=7), i-neutropenia (n=6), i-γ-GT ephezulu (n=3), i-hypokalemia (n=2). Iziguli eziyisithupha zazine-cytokine release syndrome (CRS) (G3: 1; G2: 1; G1: 4), kanti iziguli ezimbili nazo zathola i-G1 ICANS, zonke zaphela ngokuphelele ngemva kokwelashwa okunezimpawu. Okubalulekile, ngemuva kokuhlolwa okungenani okubili kwesimila, ezingu-4 zaziqinisekisile impendulo engaphelele, ezingu-3 zazinesifo esizinzile, kanti ezingu-1 zazinesifo esiqhubekayo. I-ORR ngosuku lokugcina yayingu-50%. Isikhathi esimaphakathi kuya empendulweni yokuqala kwakuyizinyanga ezingu-1.1 (1.1 kuya ku-2.2) kanti isikhathi esimaphakathi sempendulo sasiyizinyanga ezingu-5.0 (1.5 kuya ku-8.8). Iningi leziguli lisalandelwa. Lapho kuhlanganiswa idatha yomthamo ofanayo engxenyeni yesigaba soku-1, i-ORR kumthamo ongu-1.2 × 10.10kwakungu-54.5% (6/11).
Njengamanje, kusenezivivinyo eziningi zemitholampilo zobuchwepheshe obusha bokulwa nomdlavuza eShayina ezifuna iziguli. Ukubonisana ngemithi emisha kanye nobuchwepheshe, ungaxhumana noMnyango Wezizwe Ngezizwe Wesibhedlela iBeijing South Region Oncology.
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Email：myimmnet@163.com
IZINKOMBA
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
Isikhathi sokuthunyelwe: Disemba 18-2024