Iiseli ze-TAEST16001 ziiseli ze-T ezenziwe ngokwezakhi zofuzo ezibonisa i-NY-ESO-1-specific T-cell receptor (TCR) ejolise kwi-NY-ESO-1 (ebonakaliswa kuluhlu olubanzi lweethumba) kwi-positive soft tissue sarcoma (STS) kumxholo we-HLA-A*02:01.
Uphononongo lwesigaba sokuqala kwizigulane ezine-STS ephucukileyo (NCT04318964) lubonise ukhuseleko kunye nesibonakaliso sokuqala sokusebenza kakuhle kwi-ASCO 2022. Olu luphononongo oluvulekileyo, olunengalo enye, olunyusa umthamo kunye nolwandiso lokuvavanya ukhuseleko, ukunyamezeleka, i-PK, i-PD kunye nokusebenza kwangaphambili kweeseli ze-TAEST16001 kwizigulane ezine-sarcoma yezicubu ezithambileyo.
Iziphumo: Ukusukela nge-31 kaDisemba 2021, izigulane ezili-12 ezine-sarcoma yezicubu ezithambileyo eziphucukileyo zabhaliswa (M:F 7:5; ubudala obuphakathi = 37.9; iirejimeni zangaphambili eziphakathi = 2 (uluhlu 1-3)). Iiseli ze-TAEST16001 zanyamezelwa kakuhle ngaphandle kokuthintela ubuthi obunokuthintela idosi. Iziganeko ezimbi ezixelwe rhoqo zebanga ³ 3 yayiyi-lymphopenia (n = 12), i-leukopenia (n = 10), i-neutropenia (n = 11), i-anemia (n = 4), i-thrombocytopenia (n = 1), i-hypokalemia (n = 1), kunye nomkhuhlane (n = 1). Izigulane ezibini zafumana i-cytokine release syndrome (amabanga 2) kwaye zaphela emva konyango oluneempawu. Akukho namnye kwizigulane owayene-neurotoxicity, okanye iziganeko ezimbi ezinzulu ezinxulumene nokufakwa kweseli. Idosi ephezulu enyamezelweyo (MTD) ayizange ifikelelwe. Imodeli ye-PK ibonise ukuba i-Tmax yeeseli ze-TAEST16001 yayiziintsuku eziyi-6.23 emva kokufakwa kweeseli, kwaye kwakungekho budlelwane phakathi kwempendulo yeklinikhi kunye ne-Cmax/AUC0-28. Phakathi kwezigulane ezili-12 ezivavanywayo ngempumelelo, izigulane ezi-5 zazinempendulo engaphelelanga, izigulane ezi-5 zazinesifo esizinzileyo, kwaye izigulane ezi-2 zazinesifo esiqhubekayo. Izinga lokuphendula lilonke lalingama-41.7%. Ixesha eliphakathi ukuya kwimpendulo yokuqala yayiyinyanga eyi-1.9 (uluhlu, ukusuka kwi-0.9 ukuya kwi-3.0), kwaye ubude obuphakathi bempendulo yayiyiinyanga ezili-14.1 (uluhlu, ukusuka kwi-5.0 ukuya kwi-14.2).
Okuphawulekayo kukuba, isigulana i-T06 (indoda eneminyaka engama-42 ubudala), esasifumene iindlela ezimbini zonyango zangaphambili kwaye safumana i-CRS yebanga lesi-2 emva konyango lwe-TAEST16001, sabonisa impendulo engaphelelanga kwingalo ephezulu kunye nezilonda ezininzi ze-metastatic zemiphunga emva kweeveki ezi-4 zokufakwa kweseli, sagcina ngaphezulu kweenyanga ezili-14 emva konyango. Njengoko izilonda ze-metastatic zemiphunga zahlala ziyimpendulo enkulu engaphelelanga kwanangexesha lokuqhubela phambili, isigulana sanqunyulwa isilonda engalweni ephezulu ngotyando. Esinye isigulana, i-T02 (indoda eneminyaka engama-27 ubudala), esasine-myxoid liposarcoma ephindaphindayo emlenzeni wasekunene emva kotyando oluhlanu, naso sabonisa impendulo engaphelelanga kwaye sahlala ixesha elingaphezu konyaka emva konyango.
Ngowama-2024, i-American Society of Clinical Oncology (ASCO) ibike ukubapuphando lwe-hase IIA lwe-high-affinity TCR-T (TAEST16001) olujolise kwi-NY-ESO-1 kwi-soft tissue sarcoma (NCT05549921).
Iindlela: Olu luphononongo oluvulekileyo, olunengalo enye lokuvavanya ukusebenza kakuhle kunye nokhuseleko lweeseli ze-TAEST16001 kwizigulane ezine-STS ephucukileyo (NCT05549921). Izigulane ezibhalisiweyo zenze i-apheresis, iiseli zazo ze-T ezahluliweyo zanda kwi-vitro emva kokudluliselwa nge-lentiviral vector ebonisa ukuhambelana okuphezulu kwe-NY-ESO-1 TCR. Izigulane zifumene i-chemotherapy ye-lymphodepleting yeentsuku ezi-3 (i-cyclophosphamide 15 mg/kg/ngosuku kunye ne-fludarabine 20 mg/m2/ngosuku). Iiseli ze-TAEST16001 zinikwe kwi-1.2 × 1010Iiseli ezingama-± 30% (zichongiwe ngokwedatha yethu yesigaba soku-1) kwaye zifumene inaliti ye-IL-2 sc yeentsuku ezili-14. Ukusebenza kakuhle kwethagethi (ngokwe-RECIST 1.1) kumiselwe kwizinga lokuphendula ngokubanzi (ORR) = 25% kwiqela lokuqala lezigulane ezili-12.
Iziphumo: Ukusukela ngoJanuwari 2024, izigulane ezisi-8 zabhaliswa (M:F 4:4; ubudala obuphakathi: iminyaka engama-40; iindlela zangaphambili eziphakathi: 3 (uluhlu:2-5)). Iiseli ze-TAEST16001 zibonise iprofayili yokhuseleko elawulekayo ehambelana nesifundo sangaphambili sesigaba soku-1. Iziganeko ezimbi eziqhelekileyo (n>1) ezixeliweyo zebanga (G) 3 yayiyi-lymphocytopenia (n=8), ukwehla kwenani le-WBC (n=7), i-neutropenia (n=6), i-γ-GT ephezulu (n=3), i-hypokalemia (n=2). Izigulane ezithandathu zazine-cytokine release syndrome (CRS) (G3: 1; G2: 1; G1: 4), kwaye izigulane ezi-2 nazo zafumana i-G1 ICANS, zonke zaphela ngokupheleleyo emva konyango oluneempawu. Okubalulekileyo, emva kovavanyo lwe-tumor oluphindwe kabini, ezi-4 zaziqinisekisile impendulo engaphelelanga, ezi-3 zazinesifo esizinzileyo, kwaye ezi-1 zazinesifo esiqhubekayo. I-ORR ngomhla wokugqibela yayiyi-50%. Ixesha eliphakathi ukuya kwimpendulo yokuqala yayiziinyanga ezili-1.1 (1.1 ukuya kwi-2.2) kwaye ixesha eliphakathi lempendulo yayiziinyanga ezi-5.0 (1.5 ukuya kwi-8.8). Uninzi lwezigulane lusalandelelwa. Xa kuhlanganiswa idatha yedosi efanayo kwicandelo lesigaba soku-1, i-ORR kwidosi ye-1.2 × 1010yayiyi-54.5% (6/11).
Okwangoku, kusekho iimvavanyo ezininzi zeklinikhi zobuchwepheshe obutsha bokulwa nomhlaza eTshayina obufuna izigulane. Iingcebiso ngamayeza amatsha kunye nobuchwepheshe, ungaqhagamshelana neSebe leMicimbi yeZibhedlele ze-Oncology zaseBeijing South Region.
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IIREFERENSI
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
Ixesha leposi: Disemba-18-2024