Ko ngā pūtau TAEST16001 he pūtau-T autologous i hangaia ira e whakaatu ana i te kaiwhakawhiwhi pūtau-T NY-ESO-1-motuhake (TCR) tino hononga e aro ana ki te NY-ESO-1 (e whakaatuhia ana i roto i te whānuitanga o ngā pukupuku) sarcoma kiko ngohengohe pai (STS) i roto i te horopaki o te HLA-A*02:01.
I whakaatuhia e te rangahau wāhanga tuatahi mō ngā tūroro he STS matatau (NCT04318964) te haumaru me te tohu tuatahi o te whai huatanga i te ASCO 2022. He rangahau tuwhera, kotahi te ringa, he whakanui horopeta me te whakawhānui tēnei hei aromatawai i te haumaru, te manawanui, te PK, te PD me te whai huatanga tuatahi o ngā pūtau TAEST16001 i roto i ngā tūroro he sarcoma kiko ngohengohe.
Ngā Hua: I te 31 o Hakihea 2021, 12 ngā tūroro i whakaurua ki te rangahau me te sarcoma kiko ngohengohe matatau (M:F 7:5; te pakeke toharite = 37.9; ngā maimoatanga o mua = 2 (awhe 1-3)). I pai te manawanui o ngā pūtau TAEST16001, kāore he paitini e whakawhāiti ana i te horopeta. Ko ngā pānga kino o te taumata ³ 3 i pūrongohia pinepine ko te lymphopenia (n = 12), te leukopenia (n = 10), te neutropenia (n = 11), te anemia (n = 4), te thrombocytopenia (n = 1), te hypokalemia (n = 1), me te kirika (n = 1). Tokorua ngā tūroro i puta mai me te mate tuku cytokine (ngā taumata 2) ā, i ora i muri i te maimoatanga tohumate. Kāore tetahi o ngā tūroro i pāngia e te paitini io, i pāngia rānei e ngā pānga kino kino e pā ana ki te werohanga pūtau. Kāore i eke ki te horopeta manawanui mōrahi (MTD). I whakaatuhia e te whakatauira PK ko te Tmax o ngā pūtau TAEST16001 i roto i ngā rā 6.23 i muri i te werohanga o ngā pūtau, ā, kāore he hononga i waenga i te urupare haumanu me te Cmax/AUC0-28. I roto i ngā tūroro 12 ka taea te arotake i te whai huatanga, 5 ngā tūroro i whai urupare hapa, 5 ngā tūroro i whai mate pumau, ā, 2 ngā tūroro i whai mate haere tonu. Ko te reiti urupare whānui he 41.7%. Ko te wā toharite ki te urupare tuatahi he 1.9 marama (awhe, 0.9 ki te 3.0), ā, ko te roanga toharite o te urupare he 14.1 marama (awhe, 5.0 ki te 14.2).
He mea nui, ko te tūroro T06 (tāne 42-tau te pakeke), i whiwhi i ngā momo rongoā e rua i mua, ā, i pāngia e te CRS taumata 2 i muri i te maimoatanga TAEST16001, i whakaatu i tētahi urupare wāhanga o ngā whara metastatic o te ringa o runga me te maha o ngā pūkahukahu i muri i te 4 wiki o te werohanga pūtau, ā, i mau tonu mō te neke atu i te 14 marama i muri i te maimoatanga. I te mea i noho tonu ngā whara metastatic o te pūkahukahu hei urupare wāhanga pai ahakoa i te wā o te whanaketanga, i pokangahia te tūroro ki te tango i tētahi whara i te ringa o runga. Ko tētahi atu tūroro, ko T02 (tāne 27-tau te pakeke), i pāngia e te myxoid liposarcoma recurrent i te waewae matau i muri i te whiwhinga i ngā pokanga e rima, i whakaatu anō hoki i tētahi urupare wāhanga, ā, i mau tonu mō te neke atu i te 1 tau i muri i te maimoatanga.
I te tau 2024, i pūrongo te American Society of Clinical Oncology (ASCO)pTe rangahau IIA mō te TCR-T honohono-teitei (TAEST16001) e aro ana ki te NY-ESO-1 i roto i te sarcoma kiko ngohengohe (NCT05549921).
Ngā Tikanga: He rangahau tuwhera tēnei, he rangahau ringa kotahi hei aromatawai i te whai huatanga me te haumaru o ngā pūtau TAEST16001 i roto i ngā tūroro he STS matatau (NCT05549921). I whai apheresis ngā tūroro kua rēhitatia, ā, i whānui haere ō rātou pūtau-T motuhake i roto i te vitro i muri i te whakawhiti me te vector lentiviral e whakaatu ana i te NY-ESO-1 TCR he kaha te hononga. I whiwhi ngā tūroro i te chemotherapy lymphodepleting mō ngā rā e 3 (cyclophosphamide 15 mg/kg/rā me te fludarabine 20 mg/m2/rā). I tukuna ngā pūtau TAEST16001 i te 1.2 × 1010± 30% ngā pūtau (i whakatauhia mā roto i ā mātou raraunga wāhanga I) ā, i whiwhi hoki rātou i te werohanga IL-2 sc mō ngā rā 14. Ko te whai huatanga whāinga (e ai ki te RECIST 1.1) i whakatakotoria ki te reiti urupare whānui (ORR) =25% mō te rōpū wāhanga tuatahi o te 12 ngā tūroro.
Ngā Hua: I te marama o Hānuere 2024, e 8 ngā tūroro i whakaurua (M:F 4: 4; te pakeke toharite: 40 tau; ngā maimoatanga o mua: 3 (awhe: 2-5)). I whakaatuhia e ngā pūtau TAEST16001 he kōtaha haumaru ka taea te whakahaere e rite ana ki te rangahau wāhanga I o mua. Ko ngā pānga kino (n>1) taumata (G) 3 i pūrongohia ko te lymphocytopenia (n=8), te hekenga o te maha o ngā WBC (n=7), te neutropenia (n=6), te pikinga o te γ-GT (n=3), te hypokalemia (n=2). E ono ngā tūroro i pāngia e te cytokine release syndrome (CRS) (G3: 1; G2: 1; G1: 4), ā, e 2 ngā tūroro i pāngia e te G1 ICANS, i ora katoa i muri i te maimoatanga tohumate. He mea nui, i muri i te iti rawa i te rua ngā aromatawai pukupuku, e 4 i whakaū i te urupare hapa, e 3 i mate pumau, ā, e 1 i mate haere tonu. Ko te ORR i te rā kati he 50%. Ko te wā toharite ki te urupare tuatahi he 1.1 marama (1.1 ki te 2.2) ā, ko te roanga toharite o te urupare he 5.0 marama (1.5 ki te 8.8). Kei te tirotirohia tonutia te nuinga o ngā tūroro. I te wā e whakakotahihia ana ngā raraunga mō te horopeta kotahi i te wāhanga wāhanga tuatahi, ko te ORR i te horopeta o te 1.2 × 1010he 54.5% (6/11).
I tēnei wā, he maha tonu ngā whakamātautau haumanu o ngā hangarau hou hei ārai i te matepukupuku i Haina e rapu ana i ngā tūroro. Mēnā kei te hiahia koe ki te kōrero mō ngā rongoā me ngā hangarau hou, ka taea e koe te whakapā atu ki te Tari Ao o te Hōhipera Oncology Rohe Tonga o Beijing.
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NGĀ TOHUTORO
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
Wā tuku: Hakihea-18-2024