Umuti wa mbere w’ubudahangarwa bw’uturemangingo twa TCR-T mu Bushinwa wemejwe na IND (TAEST16001)

Uturemangingo twa TAEST16001 ni uturemangingo twa T twitwa autologous twitwa NY-ESO-1 (TCR) twibasira NY-ESO-1 (tugaragara mu tumori twinshi) dutera sarcoma yoroshye (STS) mu rwego rwa HLA-A*02:01.

Inyigo y’icyiciro cya mbere ku barwayi bafite STS ikomeye (NCT04318964) yagaragaje umutekano n’ikimenyetso cy’ibanze cy’uko ifite akamaro muri ASCO 2022. Iyi ni inyigo y’ingufu imwe, ifunguye, izamuka ry’umuti no kwaguka kugira ngo isuzume umutekano, kwihanganira, PK, PD n’ubushobozi bw’ibanze bw’uturemangingo twa TAEST16001 ku barwayi bafite sarcoma yoroshye.

Ibisubizo: Ku ya 31 Ukuboza 2021, abarwayi 12 bafite sarcoma yoroshye yo mu mubiri bari bariyandikishije (M:F 7:5; impuzandengo y'imyaka = 37.9; urwego rwo hagati rw'imiti yakoreshejwe = 2 (urugero rwa 1-3)). Uturemangingo twa TAEST16001 twihanganishijwe neza nta burozi bugabanya ku gipimo. Ingaruka mbi zagaragaye cyane ku rwego rwa ³ 3 ni lymphopenia (n = 12), leukopenia (n = 10), neutropenia (n = 11), anemia (n = 4), thrombocytopenia (n = 1), hypokalemia (n = 1), n'umuriro (n = 1). Abarwayi babiri bagaragayeho cytokine release syndrome (urwego rwa 2) kandi barakize nyuma yo kuvurwa ibimenyetso. Nta murwayi n'umwe wari ufite uburozi bwo mu bwonko, cyangwa ingaruka mbi zikomeye zijyanye no guterwa uturemangingo. Igipimo ntarengwa cyo kwihanganirwa (MTD) nticyagezweho. Isuzuma rya PK ryagaragaje ko Tmax ya TAEST16001 selile yari imaze iminsi 6.23 nyuma yo guterwa selile, kandi nta sano yari iri hagati y’uburyo selile zikora n’uburyo selile zikora Cmax/AUC0-28 zabayeho. Mu barwayi 12 bapimwe ubushobozi bwabo, abarwayi 5 bagaragaje uburyo selile zikora igice cy’uburyo selile zikora, abarwayi 5 bafite indwara zidahinduka, naho abarwayi 2 bagaragaza ko selile zikora buhoro buhoro. Igipimo rusange cy’uburyo selile zikora cyari 41.7%. Igihe cyo hagati cyo gutangira selile cyari amezi 1.9 (igihe cyo hagati, 0.9 na 3.0), naho igihe cyo hagati cyo gutangira selile cyari amezi 14.1 (igihe cyo hagati, 5.0 na 14.2).

Ikigaragara ni uko umurwayi T06 (umugabo w'imyaka 42), wari warahawe imiti ibiri mbere kandi akaba yarabonye CRS yo mu cyiciro cya kabiri nyuma yo kuvurwa na TAEST16001, yagaragaje uburyo igice cy’ibisebe byo hejuru y’ukuboko n’ibindi byinshi byanduye mu bihaha nyuma y’ibyumweru 4 amaze ahawe uturemangingo, agakomeza kugira uburyo igice cy’ibisebe byo hejuru y’ukuboko cyakomeje kuba igisubizo cyiza ndetse no mu gihe cyo gukomeza kwangirika, umurwayi yarabazwe agacibwa igisebe cyo hejuru y’ukuboko. Undi murwayi, T02 (umugabo w’imyaka 27), wari warasubiye kurwara myxoid liposarcoma mu kuguru kw’iburyo nyuma yo kubagwa inshuro eshanu, na we yagaragaje uburyo igice cy’ibisebe kandi yamaze umwaka urenga umwe nyuma yo kuvurwa.

Mu 2024, Ikigo cy’Abanyamerika gishinzwe kurwanya kanseri y’inkondo y’umura (ASCO) cyatangaje kopInyigo ya Hase IIA kuri TCR-T (TAEST16001) igamije kwibasira NY-ESO-1 muri sarcoma yoroshye y'uturemangingo (NCT05549921).

Uburyo: Ubu ni ubushakashatsi bwakozwe ku ruhande rumwe, bufite ikimenyetso cyo gusuzuma imikorere n'umutekano w'uturemangingo twa TAEST16001 ku barwayi bafite STS ikomeye (NCT05549921). Abarwayi biyandikishije bakorewe apheresis, uturemangingo twa T twabo twakuwemo twaguwe mu buryo bwa vitro nyuma yo guterwa hamwe na vector ya lentiviral igaragaza imbaraga nyinshi za NY-ESO-1 TCR. Abarwayi bahawe imiti ya lymphodepleting chemotherapy y'iminsi 3 (cyclophosphamide 15 mg/kg/umunsi na fludarabine 20 mg/m2/umunsi). Uturemangingo twa TAEST16001 twatanzwe kuri 1.2 × 10¹⁰± 30% by'uturemangingo (byagenwe binyuze mu makuru yacu ya phase I) kandi banatewe inshinge za IL-2 sc mu minsi 14. Ingaruka nziza (kuri RECIST 1.1) yagenwe ku gipimo rusange cy'ubutabazi (ORR) = 25% ku cyiciro cya mbere cy'abarwayi 12.

Ibisubizo: Guhera muri Mutarama 2024, abarwayi 8 biyandikishije (M:F 4:4; impuzandengo y'imyaka: imyaka 40; urwego rw'imiti yabanje: 3 (urugero: 2-5)). Uturemangingo twa TAEST16001 twagaragaje umutekano ushoboka ujyanye n'inyigo yabanje y'icyiciro cya mbere. Ingaruka mbi zisanzwe (n>1) zavuzwe ku rwego rwa 3 (G) zari lymphocytopenia (n=8), kugabanuka k'umubare wa WBC (n=7), neutropenia (n=6), kwiyongera kwa γ-GT (n=3), hypokalemia (n=2). Abarwayi batandatu bari bafite cytokine release syndrome (CRS) (G3: 1; G2: 1; G1: 4), kandi abarwayi 2 nabo bahuye na G1 ICANS, bose barakize burundu nyuma yo kuvurwa ibimenyetso. Icy'ingenzi ni uko nyuma yo gusuzuma nibura inshuro ebyiri ikibyimba, 4 bemeje ko bakira igice cy'indwara, 3 bari bafite indwara idahinduka, naho 1 yari afite indwara ikomeza kwiyongera. ORR ku itariki ntarengwa yari 50%. Igihe cyo hagati kugeza ku gisubizo cya mbere cyari amezi 1.1 (1.1 kugeza 2.2) naho igihe cyo hagati cy’igisubizo cyari amezi 5.0 (1.5 kugeza 8.8). Abarwayi benshi baracyakurikiranwa. Mu gihe cyo gukusanya amakuru y’igipimo kimwe mu gice cya mbere, ORR ku gipimo cya 1.2 × 10.¹⁰yari 54.5% (6/11).

Kugeza ubu, haracyari igeragezwa ryinshi ry’ikoranabuhanga rishya rirwanya kanseri mu Bushinwa rishaka abarwayi. Inama ku miti mishya n’ikoranabuhanga, ushobora kuvugana n’Ishami Mpuzamahanga ry’Ibitaro bya Oncology bya Beijing mu Karere k’Amajyepfo.

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INYANDIKO Z'IBIREGO

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