Lisele tsa TAEST16001 ke lisele tsa T tse entsoeng ka liphatsa tsa lefutso tse hlahisang receptor ea sele ea T e khethehileng ea NY-ESO-1 (TCR) e shebaneng le NY-ESO-1 (e hlahisoang mefuteng e mengata ea lihlahala) positive soft tissue sarcoma (STS) moelelong oa HLA-A*02:01.
Phuputso ea mohato oa I ho bakuli ba nang le STS e tsoetseng pele (NCT04318964) e bontšitse polokeho le sesupo sa pele sa katleho ho ASCO 2022. Ena ke thuto e bulehileng, e nang le letsoho le le leng, ea keketseho ea tekanyo le katoloso ho lekola polokeho, mamello, PK, PD le katleho ea pele ea lisele tsa TAEST16001 ho bakuli ba nang le sarcoma ea lisele tse bonolo.
Liphetho: Ho tloha ka la 31 Tšitoe 2021, bakuli ba 12 ba nang le sarcoma e tsoetseng pele ea lisele tse bonolo ba ile ba ngolisoa (M:F 7:5; karolelano ea lilemo = 37.9; mekhoa ea pele ea bohareng = 2 (sebaka sa 1-3)). Lisele tsa TAEST16001 li ile tsa mamelloa hantle ntle le chefo e fokotsang tekanyo. Liketsahalo tse mpe tse tlalehiloeng khafetsa tsa sehlopha sa ³ 3 e ne e le lymphopenia (n = 12), leukopenia (n = 10), neutropenia (n = 11), khaello ea mali (n = 4), thrombocytopenia (n = 1), hypokalemia (n = 1), le feberu (n = 1). Bakuli ba babeli ba ile ba hlaha ba e-na le cytokine release syndrome (likereiti tsa 2) 'me ba ile ba fela ka mor'a kalafo ea matšoao. Ha ho le ea mong oa bakuli ea neng a e-na le chefo ea methapo ea kutlo, kapa liketsahalo tse mpe tse amanang le ho kenngoa ha sele. Tekanyo e phahameng ka ho fetisisa e mamelletsoeng (MTD) ha ea ka ea fihlelloa. Tlhahlobo ea PK e bontšitse hore Tmax ea lisele tsa TAEST16001 e bile matsatsi a 6.23 kamora ho kenngoa ha lisele, 'me ho ne ho se na kamano pakeng tsa karabelo ea kliniki le Cmax/AUC0-28. Har'a bakuli ba 12 ba hlahlobang katleho, bakuli ba 5 ba bile le karabelo e sa fellang, bakuli ba 5 ba ne ba e-na le lefu le tsitsitseng, 'me bakuli ba 2 ba ne ba e-na le lefu le tsoelang pele. Sekhahla sa karabelo ka kakaretso e ne e le 41.7%. Nako e mahareng ea karabelo ea pele e ne e le likhoeli tse 1.9 (sebaka, 0.9 ho isa ho 3.0), 'me nako e mahareng ea karabelo e ne e le likhoeli tse 14.1 (sebaka, 5.0 ho isa ho 14.2).
Haholo-holo, mokuli T06 (monna ea lilemo li 42), ea neng a fumane mekhoa e 'meli ea pele ea phekolo 'me a bile le CRS ea sehlopha sa 2 kamora kalafo ea TAEST16001, o bontšitse karabelo e sa fellang ea liso tse ngata tsa matšoafo tse nang le tšoaetso ea 'mele ka mor'a libeke tse 4 tsa ho kenngoa ha sele, a boloka likhoeli tse fetang 14 kamora kalafo. Kaha liso tse nang le tšoaetso ea matšoafo li ile tsa lula e le karabelo e kholo ea karolo esita le nakong ea tsoelo-pele, mokuli o ile a etsoa opereishene ea ho ntša liso letsohong le ka holimo. Mokuli e mong, T02 (monna ea lilemo li 27), ea neng a e-na le myxoid liposarcoma e pheta-phetoang leotong le letona kamora ho etsa opereishene tse hlano, le eena o bontšitse karabelo e sa fellang 'me a tsoela pele ho feta selemo se le seng kamora kalafo.
Ka 2024, Mokhatlo oa Amerika oa Oncology ea Kliniki (ASCO) o tlalehilepPhuputso ea hae ea IIA ea TCR-T e nang le kamano e phahameng (TAEST16001) e shebaneng le NY-ESO-1 ho sarcoma ea lisele tse bonolo (NCT05549921).
Mekhoa: Ena ke phuputso e bulehileng, e nang le letsoho le le leng ho lekola katleho le polokeho ea lisele tsa TAEST16001 ho bakuli ba nang le STS e tsoetseng pele (NCT05549921). Bakuli ba ngolisitsoeng ba ile ba etsoa apheresis, lisele tsa bona tsa T tse arohaneng li ile tsa atoloha ka hare ho vitro kamora ho fetisetsoa ka vector ea lentiviral e bontšang ho ts'oaroa ho hoholo ha NY-ESO-1 TCR. Bakuli ba ile ba fuoa chemotherapy ea lymphodepleting ea matsatsi a 3 (cyclophosphamide 15 mg/kg/letsatsi le fludarabine 20 mg/m2/letsatsi). Lisele tsa TAEST16001 li ile tsa fuoa 1.2 × 10.10Lisele tse ± 30% (tse khethiloeng ka data ea rona ea mokhahlelo oa I) 'me li boetse li fumane ente ea IL-2 sc ea matsatsi a 14. Katleho ea sepheo (ho latela RECIST 1.1) e behiloe ho sekhahla sa karabelo ka kakaretso (ORR) = 25% bakeng sa sehlopha sa mohato oa pele sa bakuli ba 12.
Liphetho: Ho tloha ka Pherekhong 2024, bakuli ba 8 ba ile ba ngolisoa (M:F 4: 4; karolelano ea lilemo: lilemo tse 40; mekhoa ea pele ea kalafo e mahareng: 3 (sebaka: 2-5)). Lisele tsa TAEST16001 li bontšitse boemo ba polokeho bo laolehang bo lumellanang le thuto ea pele ea mohato oa I. Liketsahalo tse mpe tse tloaelehileng (n>1) tse tlalehiloeng sehlopheng sa 3 (G) e ne e le lymphocytopenia (n=8), palo e fokotsehileng ea WBC (n=7), neutropenia (n=6), γ-GT e phahameng (n=3), hypokalemia (n=2). Bakuli ba tšeletseng ba ne ba e-na le cytokine release syndrome (CRS) (G3: 1; G2: 1; G1: 4), 'me bakuli ba 2 le bona ba bile le G1 ICANS, kaofela ba ile ba fela ka botlalo kamora kalafo ea matšoao. Habohlokoa, kamora bonyane liteko tse peli tsa hlahala, ba 4 ba ne ba tiisitse karabelo e sa fellang, ba 3 ba ne ba e-na le lefu le tsitsitseng, 'me a le mong o ne a e-na le lefu le tsoelang pele. ORR ka letsatsi la ho qetela e ne e le 50%. Nako e mahareng ho isa karabelong ea pele e ne e le likhoeli tse 1.1 (1.1 ho isa ho 2.2) 'me nako e mahareng ea karabelo e ne e le likhoeli tse 5.0 (1.5 ho isa ho 8.8). Bakuli ba bangata ba ntse ba lateloa. Ha ho kopanngoa lintlha tsa tekanyo e tšoanang karolong ea mohato oa I, ORR ka tekanyo ea 1.2 × 1010e ne e le 54.5% (6/11).
Hona jwale, ho ntse ho na le diteko tse ngata tsa bongaka tsa mahlale a matjha a ho lwantsha kankere Chaena a batlang bakudi. Dipuisano mabapi le meriana le mahlale a matjha, o ka ikopanya le Lefapha la Matjhaba la Sepetlele sa Oncology sa Beijing Region South.
Nomoro ea mohala: 4008803716
Email：myimmnet@163.com
LITŠUPISO
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
Nako ea poso: Tshitwe-18-2024