Ko C-CAR031, he CAR-T ā-aunoa kua whakakakahuhia ki te TGFβRIIDN motuhake ki te GPC3

Ko te C-CAR031 he rongoā ā-aunoa, he mea hanga ki te GPC3, he mea hanga ki te chimeric antigen receptor T-Cell (CAR-T), e aro ana ki te HCC. E hangai ana ki tētahi CAR-T hou e aro ana ki te GPC3, i hangaia e AstraZeneca mā te whakamahi i tā rātou tūāpapa kitenga armadura dominant negative transforming growth factor-beta receptor II dominant negative (dnTGFβRII), ā, e hangaia ana e AbelZeta i Haina. Kei te whakawhanakehia te C-CAR031 i Haina i raro i tētahi whakaaetanga whakawhanake tahi i waenganui i a AbelZeta me AstraZeneca.

I te Hui-ā-Tau a ASCO 2024, ka pānuitia e AbelZeta ngā raraunga haumanu e whakaatu ana i te kaha ārai-puku tuatahi mō te C-CAR031, he GPC3 CAR-T ā-whakairoiro, i roto i ngā tūroro he mate pukupuku hepatocellular matatau.

Ngā Tikanga: Ko te whakamātautau tuatahi i roto i te tangata, he tuwhera-tapanga, e whakamahi ana i te hoahoa titration tere me te i3+3. Ko ngā tāngata GPC3+ HCC matatau i rahua i ngā maimoatanga pūnaha ≥ 1 raina i whiwhi i te werohanga kotahi o te C-CAR031 i muri i te lymphodepletion paerewa. Ko ngā pito whakamutunga matua ko te haumaru me te manawanui, ko ētahi ko te pharmacokinetics me te whai huatanga tuatahi. I whakatauria ngā pānga kino (AE) e te CTCAE 5.0, ā, i aromatawaihia te cytokine release syndrome (CRS) / te immune effector cell-associated neurotoxicity syndrome (ICANS) e ai ki ngā paearu ASTCT 2019. I aromatawaihia te urupare whāinga e te kairangahau e ai ki te RECIST 1.1.

Ngā Hua: I te 5 o Hānuere, 2024, e 24 ngā tāngata i whiwhi i te werohanga C-CAR031 i ngā taumata horopeta e 4 (DL). Ko ngā tāngata katoa he BCLC wāhanga C HCC, 83.3% (20/24) he metastasis i waho o te ate. Ko te maha toharite o ngā raina rongoā o mua he 3.5 (awhe 1-6), 23 (95.8%) ngā tāngata i whiwhi ICI (ngā aukati tirotiro ārai mate) me TKI (ngā aukati tyrosine kinase). I taea te aromatawai i ngā tāngata katoa mō te haumaru. Kāore he paitini whakawhāiti horopeta, ā, i kitea he ICANS. I kitea te CRS i roto i te 22 (91.7%) ngā tāngata me te 1 anake (4.2%) taumata (G) 3 CRS. Ko ngā AE ≥G3 tino noa ko te lymphocytopenia (100%), te neutropenia (70.8%), te thrombocytopenia (37.5%) me te whakanui transaminase (16.7%). Kotahi te tangata (4.2%) i pāngia e te G4 myelosuppression, ā, kotahi te tangata (4.2%) i pāngia e te G3 interstitial pneumonitis i te DL4 i puta mai i te G3 CRS. I taea te whakakore i ngā AE katoa. E 22 ngā tohu i taea te arotake mō te whai huatanga. I kitea te whakahekenga o te pukupuku i roto i te 90.9% o ngā tohu, ehara i te mea i roto i ngā whara o roto i te ate anake engari i waho atu hoki i te ate me te whakahekenga toharite o te 44.0% (awhe, 3.4%-94.4%). Ko te reiti whakahaere mate he 90.9%, ā, ko te reiti urupare whāinga (ORR) he 50.0% mō ngā tohu o ngā DL katoa. I roto i te DL4, ko te ORR he 57.1%.

Ngā Whakatau: I whakaatuhia e te rangahau he āhua haumaru ka taea te whakahaere, me te whakatenatena i te kaha ārai-puku o C-CAR031 i roto i ngā tūroro HCC matatau kua tino rongoatia.

"E whakatenatenahia ana mātou e ngā hua haumanu tuatahi o C-CAR031 i roto i ngā tūroro mate pukupuku ate (HCC) matatau," te kī a Tony (Bizuo) Liu, Heamana me te Tumu Whakarae o AbelZeta. "Ko ngā raraunga tuatahi i whakaaturia i tēnei rā e whakarato ana i te taunakitanga whai hua hei tautuhi anō i ngā tauira rongoā i roto i te HCC me ētahi atu pukupuku totoka e whakaatu ana i te GPC3."

I kī te Kairangahau Matua (PI) o te rangahau, a Ahorangi Tingbo Liang o te Hōhipera Hononga Tuatahi o Te Whare Wānanga o Zhejiang, "I whakaatu a C-CAR031 i te āhua haumaru pai me te whai huatanga pai i roto i ngā tūroro mate pukupuku hepatocellular wāhanga mutunga, he iti noa iho ngā kōwhiringa maimoatanga e wātea ana. Ko te whakahekenga o te pukupuku i kitea i roto i te nuinga/tino nui (91.3%) o ngā tūroro e kī ana he kaha tō C-CAR031 ki te kawe mai i te uara haumanu me te tuku tumanako ki ēnei tūroro."

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.I te Hui-ā-Tau a ASCO 2024, i panuitia e AbelZeta ngā raraunga haumanu e whakaatu ana i te kaha ārai-puku tuatahi mō te C-CAR031, he GPC3 CAR-T ā-whakairoiro, i roto i ngā tūroro he mate pukupuku hepatocellular matatau.

2.Te rangahau Wāhanga I o C-CAR031, he CAR-T ā-roto e hāngai ana ki te GPC3, he mea hanga ki te TGFβRIIDN, i roto i ngā tūroro e pangia ana e te mate pukupuku ate (HCC) matatau. | Journal of Clinical Oncology (ascopubs.org)