Maselo a TAEST16001 ndi maselo a T opangidwa mwa majini omwe amawonetsa mgwirizano wapamwamba wa NY-ESO-1-specific T-cell receptor (TCR) womwe umayang'ana NY-ESO-1 (womwe umapezeka m'mitundu yosiyanasiyana ya zotupa) positive soft tissue sarcoma (STS) potengera HLA-A*02:01.
Kafukufuku wa gawo loyamba mwa odwala omwe ali ndi STS yapamwamba (NCT04318964) adawonetsa chitetezo ndi chisonyezero choyambirira cha kugwira ntchito bwino pa ASCO 2022. Uwu ndi kafukufuku wotseguka, wokhudza dzanja limodzi, kuchuluka kwa mlingo ndi kukula kuti awone chitetezo, kulekerera, PK, PD ndi mphamvu yoyamba ya maselo a TAEST16001 mwa odwala omwe ali ndi sarcoma yofewa.
Zotsatira: Pofika pa 31 Disembala 2021, odwala 12 omwe anali ndi sarcoma yofewa kwambiri adalembedwa (M:F 7:5; apakati pa zaka = 37.9; apakati pa regimen yoyamba = 2 (kuyambira 1-3)). Maselo a TAEST16001 adalekerera bwino popanda kuchepetsa poizoni wochepa pa mlingo. Zochitika zoyipa zomwe zimanenedwa kwambiri pa giredi ³ 3 zinali lymphopenia (n = 12), leukopenia (n = 10), neutropenia (n = 11), kuchepa kwa magazi m'thupi (n = 4), thrombocytopenia (n = 1), hypokalemia (n = 1), ndi malungo (n = 1). Odwala awiri adapezeka ndi cytokine release syndrome (giredi 2) ndipo adachira atalandira chithandizo chamankhwala. Palibe wodwala aliyense amene anali ndi vuto la neurotoxicity, kapena zochitika zoyipa zokhudzana ndi kulowetsedwa kwa maselo. Mlingo wapamwamba kwambiri wololera (MTD) sunafike. Kuyesa kwa PK kunasonyeza kuti Tmax ya maselo a TAEST16001 inali patatha masiku 6.23 kuchokera pamene maselo analowetsedwa, ndipo panalibe ubale pakati pa kuyankha kwachipatala ndi Cmax/AUC0-28. Pakati pa odwala 12 omwe ankayesa kugwira ntchito bwino, odwala 5 anali ndi yankho lochepa, odwala 5 anali ndi matenda okhazikika, ndipo odwala awiri anali ndi matenda opitirira muyeso. Chiŵerengero chonse cha kuyankha chinali 41.7%. Nthawi yapakati mpaka kuyankha koyamba inali miyezi 1.9 (kuyambira, 0.9 mpaka 3.0), ndipo nthawi yapakati ya kuyankha inali miyezi 14.1 (kuyambira, 5.0 mpaka 14.2).
Chochititsa chidwi n'chakuti, wodwala T06 (mwamuna wazaka 42), yemwe adalandira njira ziwiri zochiritsira kale ndipo adalandira chithandizo cha giredi 2 CRS atalandira chithandizo cha TAEST16001, adawonetsa kuyankha pang'ono kwa mkono wapamwamba ndi zilonda zambiri za m'mapapo pambuyo pa milungu 4 atalandira chithandizo cha maselo, zomwe zidapitilira miyezi 14 atalandira chithandizo. Popeza zilonda za m'mapapo zomwe zidafalikira sizinali bwino ngakhale panthawi yomwe matendawa adakula, wodwalayo adachitidwa opaleshoni yochotsa chilonda m'manja. Wodwala wina, T02 (mwamuna wazaka 27), yemwe adachira myxoid liposarcoma m'mwendo wakumanja atachitidwa opaleshoni zisanu, adawonetsanso kuyankha pang'ono ndipo adakhala ndi chithandizo kwa zaka zoposa chaka chimodzi pambuyo pa chithandizo.
Mu 2024, bungwe la American Society of Clinical Oncology (ASCO) linanena kuti:pKafukufuku wa IIA wa TCR-T (TAEST16001) wokhudzana ndi NY-ESO-1 mu sarcoma yofewa ya minofu (NCT05549921).
Njira: Iyi ndi kafukufuku wotseguka, wokhala ndi dzanja limodzi kuti awone momwe maselo a TAEST16001 amagwirira ntchito komanso chitetezo chake mwa odwala omwe ali ndi STS yapamwamba (NCT05549921). Odwala omwe adalembetsa adachitidwa opaleshoni ya apheresis, maselo awo a T omwe adachotsedwa adakula mu vitro atapatsidwa chithandizo ndi lentiviral vector yomwe ikuwonetsa mphamvu yayikulu ya NY-ESO-1 TCR. Odwala adalandira chemotherapy ya lymphodepleting ya masiku atatu (cyclophosphamide 15 mg/kg/tsiku ndi fludarabine 20 mg/m2/tsiku). Maselo a TAEST16001 adapatsidwa pa 1.2 × 10.10Maselo ± 30% (omwe adatsimikiziridwa kudzera mu deta yathu ya gawo I) ndipo adalandiranso jakisoni wa IL-2 sc wa masiku 14. Kugwira ntchito bwino kwa cholinga (malinga ndi RECIST 1.1) kunayikidwa pamlingo wonse woyankha (ORR) = 25% pa gulu loyamba la odwala 12.
Zotsatira: Pofika mu Januwale 2024, odwala 8 adalembetsa (M:F 4:4; zaka zapakati: zaka 40; njira zapakati zochiritsira: 3 (kuyambira: 2-5)). Maselo a TAEST16001 adawonetsa chitetezo chodalirika chogwirizana ndi kafukufuku wakale wa gawo loyamba. Zochitika zoyipa zomwe zimafala kwambiri (n>1) zomwe zidanenedwa kuti ndi kalasi (G) 3 zinali lymphocytopenia (n=8), kuchepa kwa chiwerengero cha WBC (n=7), neutropenia (n=6), kuchuluka kwa γ-GT (n=3), hypokalemia (n=2). Odwala asanu ndi mmodzi anali ndi cytokine release syndrome (CRS) (G3: 1; G2: 1; G1: 4), ndipo odwala awiri adakumananso ndi G1 ICANS, onse adachira kwathunthu atalandira chithandizo cha zizindikiro. Chofunika kwambiri, pambuyo pa kuwunika kawiri kwa chotupa, 4 adatsimikizira kuyankha pang'ono, 3 anali ndi matenda okhazikika, ndipo 1 anali ndi matenda opitilira. ORR pa tsiku lomaliza linali 50%. Nthawi yapakati yoyambira kuyankha inali miyezi 1.1 (1.1 mpaka 2.2) ndipo nthawi yapakati yoyankha inali miyezi 5.0 (1.5 mpaka 8.8). Odwala ambiri akutsatiridwabe. Mukaphatikiza deta ya mlingo womwewo mu gawo loyamba, ORR pa mlingo wa 1.2 × 10.10anali 54.5% (6/11).
Pakadali pano, pali mayesero ambiri azachipatala a ukadaulo watsopano wothana ndi khansa ku China omwe akufuna odwala. Mukafunsira mankhwala ndi ukadaulo watsopano, mutha kulumikizana ndi Dipatimenti Yapadziko Lonse ya Chipatala cha Oncology ku Beijing South Region.
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MAWU OTHANDIZA
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
Nthawi yotumizira: Disembala 18-2024