Cov hlwb TAEST16001 yog cov hlwb T autologous uas tau tsim los ntawm kev hloov pauv caj ces uas qhia txog cov hlwb T-cell receptor (TCR) uas muaj kev sib raug zoo heev uas tsom mus rau NY-ESO-1 (qhia tawm hauv ntau hom qog nqaij hlav) uas muaj cov qog nqaij mos mos (STS) hauv cov ntsiab lus ntawm HLA-A*02:01.
Ib txoj kev tshawb fawb theem I ntawm cov neeg mob uas muaj STS siab heev (NCT04318964) tau ua pov thawj txog kev nyab xeeb thiab qhov qhia ua ntej ntawm kev ua haujlwm ntawm ASCO 2022. Qhov no yog kev tshawb fawb qhib, ib sab caj npab, kev nce koob tshuaj thiab kev nthuav dav los ntsuas kev nyab xeeb, kev kam rau siab, PK, PD thiab kev ua haujlwm thawj zaug ntawm TAEST16001 hlwb hauv cov neeg mob uas muaj cov nqaij mos sarcoma.
Cov Txiaj Ntsig: Txij li hnub tim 31 Lub Kaum Ob Hlis 2021, muaj 12 tus neeg mob uas muaj mob qog nqaij mos mos tau raug sau npe (M:F 7:5; hnub nyoog nruab nrab = 37.9; cov txheej txheem ua ntej nruab nrab = 2 (ntau yam 1-3)). Cov hlwb TAEST16001 tau txais kev pom zoo zoo nrog tsis muaj kev txwv tsis pub muaj tshuaj lom. Cov xwm txheej tsis zoo qib ³ 3 feem ntau tau tshaj tawm yog lymphopenia (n = 12), leukopenia (n = 10), neutropenia (n = 11), anemia (n = 4), thrombocytopenia (n = 1), hypokalemia (n = 1), thiab kub taub hau (n = 1). Ob tus neeg mob tau nthuav tawm nrog cytokine tso tawm syndrome (qib 2) thiab daws tau tom qab kev kho mob cov tsos mob. Tsis muaj ib tus neeg mob muaj neurotoxicity, lossis cov xwm txheej tsis zoo loj ntsig txog kev txhaj tshuaj ntawm tes. Qhov tshuaj ntau tshaj plaws uas tau txais kev pom zoo (MTD) tsis tau mus txog. Kev ua qauv PK qhia tau hais tias Tmax ntawm cov hlwb TAEST16001 yog 6.23 hnub tom qab cov hlwb infusion, thiab tsis muaj kev sib raug zoo ntawm kev teb hauv kev kho mob thiab Cmax / AUC0-28. Ntawm 12 tus neeg mob uas ntsuas tau qhov ua tau zoo, 5 tus neeg mob muaj kev teb ib nrab, 5 tus neeg mob muaj tus kab mob ruaj khov, thiab 2 tus neeg mob muaj tus kab mob nce zuj zus. Tus nqi teb tag nrho yog 41.7%. Lub sijhawm nruab nrab rau kev teb thawj zaug yog 1.9 lub hlis (ntau yam, 0.9 txog 3.0), thiab lub sijhawm nruab nrab ntawm kev teb yog 14.1 lub hlis (ntau yam, 5.0 txog 14.2).
Qhov tseem ceeb, tus neeg mob T06 (txiv neej hnub nyoog 42 xyoo), uas tau txais ob txoj kev kho mob ua ntej thiab tau ntsib qib 2 CRS tom qab kev kho mob TAEST16001, tau pom tias muaj kev teb ib nrab ntawm sab caj npab thiab ntau qhov mob kis mus rau lub ntsws tom qab 4 lub lis piam ntawm kev txhaj tshuaj cell, tswj tau ntau dua 14 lub hlis tom qab kev kho mob. Vim tias cov mob kis mus rau lub ntsws tseem yog ib qho kev teb zoo ib nrab txawm tias thaum lub sijhawm nce qib, tus neeg mob tau phais mob ntawm qhov mob hauv sab caj npab. Lwm tus neeg mob, T02 (txiv neej hnub nyoog 27 xyoo), uas rov qab muaj myxoid liposarcoma hauv ceg sab xis tom qab tau txais tsib qhov kev phais, kuj tau pom tias muaj kev teb ib nrab thiab tau txhawb nqa ntau dua 1 xyoos tom qab kev kho mob.
Xyoo 2024, American Society of Clinical Oncology (ASCO) tau tshaj tawm tiaspKev tshawb fawb hase IIA ntawm high-affinity TCR-T (TAEST16001) tsom mus rau NY-ESO-1 hauv cov nqaij mos sarcoma (NCT05549921).
Txoj Kev: Qhov no yog kev tshawb fawb qhib-labeled, ib sab caj npab los ntsuas qhov ua tau zoo thiab kev nyab xeeb ntawm TAEST16001 hlwb hauv cov neeg mob uas muaj STS siab heev (NCT05549921). Cov neeg mob uas tau sau npe tau ua apheresis, lawv cov T hlwb cais tau nthuav dav hauv vitro tom qab transduction nrog lub lentiviral vector qhia txog kev sib raug zoo NY-ESO-1 TCR. Cov neeg mob tau txais 3-hnub lymphodepleting chemotherapy (cyclophosphamide 15 mg / kg / hnub thiab fludarabine 20 mg / m2 / hnub). TAEST16001 hlwb tau muab rau ntawm 1.2 × 1010± 30% cov hlwb (txiav txim siab los ntawm peb cov ntaub ntawv theem I) thiab lawv kuj tau txais 14-hnub IL-2 sc txhaj tshuaj. Lub hom phiaj ua haujlwm tau zoo (ib RECIST 1.1) tau teeb tsa ntawm qhov kev teb tag nrho (ORR) = 25% rau thawj theem ntawm 12 tus neeg mob.
Cov Txiaj Ntsig: Txij li Lub Ib Hlis 2024, muaj 8 tus neeg mob tau sau npe (M:F 4: 4; hnub nyoog nruab nrab: 40 xyoo; cov txheej txheem ua ntej nruab nrab: 3 (ntau yam: 2-5)). TAEST16001 hlwb tau qhia txog cov ntaub ntawv kev nyab xeeb uas tswj tau zoo ib yam li kev kawm theem I yav dhau los. Cov xwm txheej tsis zoo uas tshwm sim feem ntau (n> 1) tau tshaj tawm qib (G) 3 yog lymphocytopenia (n = 8), txo qis WBC suav (n = 7), neutropenia (n = 6), nce γ-GT (n = 3), hypokalemia (n = 2). Rau tus neeg mob muaj cytokine tso tawm syndrome (CRS) (G3: 1; G2: 1; G1: 4), thiab 2 tus neeg mob kuj tau ntsib G1 ICANS, txhua tus tau daws tag nrho tom qab kev kho mob cov tsos mob. Qhov tseem ceeb, tom qab tsawg kawg yog ob qhov kev ntsuam xyuas qog, 4 tau lees paub qhov teb ib nrab, 3 muaj kab mob ruaj khov, thiab 1 muaj kab mob nce qib. ORR ntawm hnub txiav tawm yog 50%. Lub sijhawm nruab nrab rau kev teb thawj zaug yog 1.1 lub hlis (1.1 txog 2.2) thiab lub sijhawm nruab nrab ntawm kev teb yog 5.0 lub hlis (1.5 txog 8.8). Feem ntau cov neeg mob tseem raug saib xyuas. Thaum muab cov ntaub ntawv rau tib koob tshuaj hauv theem I, ORR ntawm koob tshuaj ntawm 1.2 × 1010yog 54.5% (6/11).
Tam sim no, tseem muaj ntau qhov kev sim tshuaj kho mob qog noj ntshav tshiab hauv Suav teb nrhiav cov neeg mob. Kev sab laj txog cov tshuaj tshiab thiab cov thev naus laus zis, koj tuaj yeem tiv tauj Beijing South Region Oncology Hospital International Department.
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COV LUS QHIA
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
Lub sijhawm tshaj tawm: Lub Kaum Ob Hlis-18-2024