Masero eTAEST16001 masero eT akagadziriswa majini anoratidza hukama hwakakura hweNY-ESO-1-specific T-cell receptor (TCR) inotarisa NY-ESO-1 (inoratidzwa mumabundu akasiyana-siyana) positive soft tissue sarcoma (STS) muchimiro cheHLA-A*02:01.
Chidzidzo chechikamu chekutanga chevarwere vane STS yepamusoro (NCT04318964) chakaratidza kuchengetedzeka uye chiratidzo chekutanga chekushanda zvakanaka paASCO 2022. Ichi chidzidzo chakavhurika, cheruoko rumwe chete, kuwedzera kwedosi uye kuwedzera kwemasero kuti vaongorore kuchengetedzeka, kushivirira, PK, PD uye kushanda kwekutanga kwemasero eTAEST16001 muvarwere vane sarcoma yetishu yakapfava.
Mhedzisiro: Kubva musi wa31 Zvita 2021, varwere gumi nevaviri vane sarcoma yemapfupa akapfava vakanyoreswa (M:F 7:5; zera repakati = 37.9; regimen yapfuura = 2 (range 1-3)). Masero eTAEST16001 akashivirira zvakanaka pasina chepfu inodzivisa dose. Zviitiko zvakaipa zvegiredhi ³ 3 zvakanyanya kutaurwa zvaive lymphopenia (n = 12), leukopenia (n = 10), neutropenia (n = 11), anemia (n = 4), thrombocytopenia (n = 1), hypokalemia (n = 1), uye fivha (n = 1). Varwere vaviri vakaonekwa vaine cytokine release syndrome (giredhi 2) uye vakapera mushure mekurapwa nezviratidzo. Hapana kana mumwe wevarwere aiva ne neurotoxicity, kana zviitiko zvakakomba zvine chekuita nekuiswa kwemasero. Dose yakanyanya kutenderwa (MTD) haina kuwanikwa. Kuenzanisa kwePK kwakaratidza kuti Tmax yemasero eTAEST16001 yaive mazuva 6.23 mushure mekuiswa kwemasero, uye pakanga pasina hukama pakati pemhinduro yekiriniki neCmax/AUC0-28. Pakati pevarwere gumi nevaviri vaiongororwa kushanda zvakanaka, varwere vashanu vaive nemhinduro isina kukwana, varwere vashanu vaive nechirwere chakagadzikana, uye varwere vaviri vaive nechirwere chinopfuurira. Mwero wemhinduro yese waive 41.7%. Nguva yepakati kusvika kumhinduro yekutanga yaive mwedzi 1.9 (nguva, 0.9 kusvika 3.0), uye nguva yepakati yekupindura yaive mwedzi 14.1 (nguva, 5.0 kusvika 14.2).
Zvinonyanya kukosha kuti murwere T06 (murume ane makore 42 okuberekwa), uyo akanga amborapwa kaviri uye akawana CRS yegiredhi rechipiri mushure mekurapwa kweTAEST16001, akaratidza mhinduro shoma yeruwoko rwepamusoro uye maronda akawanda emapapu mushure memavhiki mana ekurapwa kwemasero, achiramba aine mhinduro yakanaka yeruwoko kunyangwe panguva yekurapwa, murwere akavhiyiwa kubviswa ronda muruoko rwepamusoro. Mumwe murwere, T02 (murume ane makore 27 okuberekwa), uyo akadzokorora myxoid liposarcoma mugumbo rekurudyi mushure mekuvhiyiwa kashanu, akaratidzawo mhinduro shoma uye akaramba aine mhinduro kweanopfuura gore mushure mekurapwa.
Muna 2024, sangano reAmerican Society of Clinical Oncology (ASCO) rakashuma kutipChidzidzo cheIIA che high-affinity TCR-T (TAEST16001) chinotarisa NY-ESO-1 mu soft tissue sarcoma (NCT05549921).
Nzira: Iyi iongororo yakavhurika, ine ruoko rumwe chete yekuongorora kushanda zvakanaka uye kuchengetedzeka kwemasero eTAEST16001 muvarwere vane STS yepamusoro (NCT05549921). Varwere vakanyoreswa vakaitwa apheresis, masero avo eT akaparadzaniswa akawedzera mu vitro mushure mekuwedzerwa ne lentiviral vector inoratidza hukama hwakanyanya NY-ESO-1 TCR. Varwere vakapihwa chemotherapy yemazuva matatu ye lymphodepleting (cyclophosphamide 15 mg/kg/zuva uye fludarabine 20 mg/m2/zuva). Masero eTAEST16001 akapihwa pa 1.2 × 1010Masero ± 30% (akaongororwa kuburikidza nedata redu rechikamu chekutanga) uye vakabayiwawo jekiseni reIL-2 sc kwemazuva gumi nemana. Kushanda zvakanaka kwechinangwa (pamusana peRECIST 1.1) kwakagadzwa pahuwandu hwemhinduro (ORR) = 25% yeboka rekutanga revarwere gumi nevaviri.
Mhedzisiro: Kubva muna Ndira 2024, varwere vasere vakanyoreswa (M:F 4: 4; avhareji yezera: makore makumi mana; avhareji yemishonga yekare: 3 (range: 2-5)). Masero eTAEST16001 akaratidza kuchengetedzeka kunogoneka kunoenderana nekudzidza kwechikamu chekutanga chekare. Zviitiko zvakashata zvakajairika (n>1) zvakashumwa zvegiredhi (G) 3 zvaive lymphocytopenia (n= 8), kudzikira kwehuwandu hweWBC (n= 7), neutropenia (n= 6), yakakwira γ-GT (n= 3), hypokalemia (n= 2). Varwere vatanhatu vaive ne cytokine release syndrome (CRS) (G3: 1; G2: 1; G1: 4), uye varwere vaviri vakasanganawo neG1 ICANS, vese vakapera zvachose mushure mekurapwa nezviratidzo. Zvakakosha, mushure mekuongororwa kwebundu kaviri, vana vakaratidza kupindura kwechikamu, vatatu vaive nechirwere chakagadzikana, uye mumwe aive nechirwere chinopfuurira. ORR pazuva rekupedzisira yaive 50%. Nguva yepakati kusvika pakupindura kwekutanga yaive mwedzi 1.1 (1.1 kusvika 2.2) uye nguva yepakati yekupindura yaive mwedzi 5.0 (1.5 kusvika 8.8). Varwere vazhinji vachiri kuteverwa. Pakuunganidza data remushonga mumwe chete muchikamu chekutanga, ORR pachiyero che1.2 × 10.10yaive 54.5% (6/11).
Parizvino, kuchine miedzo yakawanda yekiriniki yehunyanzvi hutsva hwekurwisa gomarara muChina huri kutsvaga varwere. Kana muchida kubvunzana nezvemishonga mitsva netekinoroji, munogona kubata Dhipatimendi reBeijing South Region Oncology Hospital International.
Nhamba yefoni: 4008803716
Email：myimmnet@163.com
ZVINOTAURWA
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
Nguva yekutumira: Zvita-18-2024