Unugyada TAEST16001 waa unugyo T oo iskiis u shaqeeya oo hidde ahaan loo sameeyay oo muujiya soo-dhoweeyaha T-cell-ka NY-ESO-1-gaarka ah (TCR) oo bartilmaameedsanaya NY-ESO-1 (oo lagu muujiyo noocyo badan oo burooyinka ah) oo ah sarcoma unug jilicsan oo togan (STS) marka loo eego HLA-A*02:01.
Daraasad heer 1 ah oo lagu sameeyay bukaanada qaba STS-da horumarsan (NCT04318964) ayaa muujisay badbaadada iyo tilmaam hordhac ah oo ku saabsan waxtarka ASCO 2022. Kani waa daraasad furan oo gacan keliya ah, kor u kaca qiyaasta iyo ballaarinta si loo qiimeeyo badbaadada, dulqaadka, PK, PD iyo waxtarka hordhaca ah ee unugyada TAEST16001 ee bukaanada qaba sarcoma unugyada jilicsan.
Natiijooyinka: Laga bilaabo 31 Diseembar 2021, 12 bukaan oo qaba kansarka unugyada jilicsan ee horumarsan ayaa la diiwaan geliyay (M:F 7:5; celceliska da'da = 37.9; celceliska hore ee daawooyinka = 2 (inta u dhaxaysa 1-3)). Unugyada TAEST16001 si fiican ayaa loo dulqaatay iyada oo aan lahayn sunta xaddidaysa qiyaasta. Dhacdooyinka xun ee ugu badan ee la soo sheego ee heerka ³ 3 waxay ahaayeen lymphopenia (n = 12), leukopenia (n = 10), neutropenia (n = 11), dhiig la'aan (n = 4), thrombocytopenia (n = 1), hypokalemia (n = 1), iyo qandho (n = 1). Laba bukaan ayaa la kulmay cudurka sii deynta cytokine (fasallada 2) waxaana la xaliyay ka dib daaweynta calaamadaha. Midna bukaannada ma lahayn sunta neerfaha, ama dhacdooyin halis ah oo la xiriira gelinta unugyada. Qiyaasta ugu badan ee la dulqaatay (MTD) lama gaarin. Qaabaynta PK waxay muujisay in Tmax ee unugyada TAEST16001 ay ahaayeen 6.23 maalmood ka dib markii unugyada la geliyay, mana jirin wax xiriir ah oo u dhexeeya jawaabta kiliinikada iyo Cmax/AUC0-28. 12 bukaan oo la qiimeyn karo waxtarka, 5 bukaan ayaa jawaab celin qayb ah helay, 5 bukaan ayaa qabay cudur deggan, iyo 2 bukaan ayaa qabay cudur sii socda. Heerka jawaab celinta guud wuxuu ahaa 41.7%. Waqtiga dhexdhexaadka ah ee jawaab celinta bilowga ah wuxuu ahaa 1.9 bilood (cadadka, 0.9 ilaa 3.0), muddada dhexdhexaadka ahna waxay ahayd 14.1 bilood (cadadka, 5.0 ilaa 14.2).
Waxaa xusid mudan, bukaanka T06 (lab ah oo 42 jir ah), kaasoo helay laba saf oo hore oo daaweyn ah isla markaana la kulmay heerka 2aad ee CRS ka dib daaweynta TAEST16001, wuxuu muujiyay jawaab qayb ah oo ka timid gacanta sare iyo dhaawacyo badan oo sambabada ah ka dib 4 toddobaad oo lagu shubay unugyada, isagoo sii wata in ka badan 14 bilood daaweynta ka dib. Maadaama dhaawacyada sambabada ee faafa ay ahaayeen jawaab celin qayb ahaan oo weyn xitaa xilligii uu sii socday, bukaanku wuxuu maray qalliin looga saaray nabar gacanta sare. Bukaan kale, T02 (lab ah oo 27 jir ah), oo ku dhacay myxoid liposarcoma oo soo noqnoqda lugta midig ka dib markii uu helay shan qalliin, ayaa sidoo kale muujiyay jawaab qayb ah wuxuuna la kulmay in ka badan 1 sano daaweynta ka dib.
Sannadkii 2024, Ururka Mareykanka ee Cudurrada Oncology (ASCO) ayaa soo sheegaypDaraasadda IIA ee ku saabsan xiriirka sare ee TCR-T (TAEST16001) oo lagu bartilmaameedsanayo NY-ESO-1 ee kansarka unugyada jilicsan (NCT05549921).
Hababka: Kani waa daraasad furan oo hal gacan ah si loo qiimeeyo waxtarka iyo badbaadada unugyada TAEST16001 ee bukaanada qaba STS-da horumarsan (NCT05549921). Bukaannada la diiwaangeliyey waxay mareen apheresis, unugyadooda T ee go'doonsan ayaa ku balaartay in vitro ka dib markii la tallaalay iyadoo la adeegsanayo vector lentiviral ah oo muujinaya xiriir sare NY-ESO-1 TCR. Bukaannada waxay qaateen kiimoterabiga 3-maalmood ee lymphodepleting (cyclophosphamide 15 mg/kg/maalintii iyo fludarabine 20 mg/m2/maalintii). Unugyada TAEST16001 waxaa lagu siiyay 1.2 × 1010± 30% unugyo (oo lagu go'aamiyay xogta wejiga I) waxayna sidoo kale heleen duritaan IL-2 sc ah oo 14-maalmood ah. Waxtarka bartilmaameedka (sida RECIST 1.1) waxaa lagu dejiyay heerka guud ee jawaabta (ORR) = 25% kooxda heerka koowaad ee 12 bukaan.
Natiijooyinka: Laga bilaabo Janaayo 2024, 8 bukaan ayaa la diiwaangeliyey (M:F 4: 4; celceliska da'da: 40 sano; celceliska nidaamyada hore: 3 (kala duwanaanshaha: 2-5)). Unugyada TAEST16001 waxay muujiyeen muuqaal badbaado oo la maarayn karo oo la jaan qaadaya daraasaddii hore ee marxaladda I. Dhacdooyinka xun ee caadiga ah (n>1) ee la soo sheegay ee darajada (G) 3 waxay ahaayeen lymphocytopenia (n=8), tirada WBC oo hoos u dhacday (n=7), neutropenia (n=6), γ-GT oo kor u kacay (n=3), hypokalemia (n=2). Lix bukaan ayaa qabay cudurka sii deynta cytokine (CRS) (G3: 1; G2: 1; G1: 4), 2 bukaan ayaa sidoo kale la kulmay G1 ICANS, dhammaantoodna si buuxda ayaa loo xalliyey ka dib daaweynta calaamadaha. Waxaa muhiim ah, ka dib ugu yaraan laba qiimeyn oo buro ah, 4 waxay xaqiijiyeen jawaab qayb ahaan ah, 3 waxay lahaayeen cudur deggan, 1na waxay lahaayeen cudur sii socda. ORR-ga taariikhda go'itaanka wuxuu ahaa 50%. Waqtiga dhexdhexaadka ah ee jawaab celinta bilowga ah wuxuu ahaa 1.1 bilood (1.1 ilaa 2.2) muddada dhexdhexaadka ah ee jawaabtuna waxay ahayd 5.0 bilood (1.5 ilaa 8.8). Bukaannada badankood wali waa la socda. Marka la isku darayo xogta qiyaasta isku midka ah ee qaybta wejiga I, ORR qiyaasta 1.2 × 1010waxay ahayd 54.5% (6/11).
Waqtigan xaadirka ah, waxaa weli jira tijaabooyin caafimaad oo badan oo ku saabsan teknoolojiyada cusub ee ka hortagga kansarka ee Shiinaha oo raadinaya bukaanno. La-tashi ku saabsan daawooyinka cusub iyo teknoolojiyada, waxaad la xiriiri kartaa Waaxda Caalamiga ah ee Isbitaalka Oncology ee Gobolka Koonfureed ee Beijing.
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TIXRAACYADA
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
Waqtiga boostada: Diseembar-18-2024