Mkpụrụ ndụ TAEST16001 bụ mkpụrụ ndụ T nke e mepụtara site na mkpụrụ ndụ ihe nketa nke na-egosipụta ihe nnabata T-cell NY-ESO-1-specific (TCR) nke nwere njikọ chiri anya na NY-ESO-1 (nke a na-egosipụta n'ọtụtụ etuto ahụ) nke nwere sarcoma anụ ahụ dị nro (STS) dị mma dịka HLA-A*02:01 si kwuo.
Nnyocha nke usoro nke mbụ n'ime ndị ọrịa nwere STS dị elu (NCT04318964) gosiri nchekwa na ihe ngosi mbụ nke irè na ASCO 2022. Nke a bụ ọmụmụ ihe mepere emepe, otu ogwe aka, mmụba dose na mmụba iji nyochaa nchekwa, ndidi, PK, PD na irè mbụ nke mkpụrụ ndụ TAEST16001 na ndị ọrịa nwere sarcoma anụ ahụ dị nro.
Nsonaazụ: Site na Disemba 31, 2021, e debara aha ndị ọrịa 12 nwere sarcoma anụ ahụ dị nro (M:F 7:5; afọ nkezi = 37.9; usoro ọgwụgwọ etiti = 2 (oke 1-3)). E nyere mkpụrụ ndụ TAEST16001 nke ọma na-enweghị nsí na-egbochi dose. Ihe omume ọjọọ ndị a na-akọkarị na ọkwa ³ 3 bụ lymphopenia (n = 12), leukopenia (n = 10), neutropenia (n = 11), anaemia (n = 4), thrombocytopenia (n = 1), hypokalemia (n = 1), na ahụ ọkụ (n = 1). Ndị ọrịa abụọ nwere ọrịa cytokine release syndrome (klas 2) ma gwọọ ha mgbe a gwọchara ha. Ọ dịghị onye n'ime ndị ọrịa ahụ nwere neurotoxicity, ma ọ bụ ihe omume ọjọọ dị njọ metụtara ntinye mkpụrụ ndụ. Erughị oke dose a na-anabata (MTD). Nlereanya PK gosiri na Tmax nke mkpụrụ ndụ TAEST16001 dị ụbọchị 6.23 mgbe a gbasasịrị mkpụrụ ndụ ahụ, ọ dịghịkwa mmekọrịta dị n'etiti nzaghachi ahụike na Cmax/AUC0-28. N'ime ndị ọrịa 12 a na-enyocha arụmọrụ ha, ndị ọrịa 5 nwere nzaghachi nke ọma, ndị ọrịa 5 nwere ọrịa kwụsiri ike, na ndị ọrịa 2 nwere ọrịa na-aga n'ihu. Ọnụego nzaghachi zuru oke bụ 41.7%. Oge etiti maka nzaghachi mbụ bụ ọnwa 1.9 (oke, 0.9 ruo 3.0), oge etiti nke nzaghachi bụ ọnwa 14.1 (oke, 5.0 ruo 14.2).
Ihe pụrụ iche bụ na onye ọrịa T06 (nwoke dị afọ 42), onye natara ọgwụgwọ abụọ gara aga ma nwee ahụmịhe na ọkwa nke abụọ nke CRS mgbe ọgwụgwọ TAEST16001 gasịrị, gosipụtara mmeghachi omume nke ogwe aka elu na ọtụtụ ọnya akpa ume mgbe izu anọ nke ntinye mkpụrụ ndụ gasịrị, na-anọgide na-enwe ihe karịrị ọnwa 14 mgbe ọgwụgwọ gasịrị. Ebe ọ bụ na ọnya akpa ume nọgidere bụrụ nnukwu nzaghachi akụkụ ọbụlagodi n'oge ọganihu ahụ, a wakporo onye ọrịa ahụ n'ime ogwe aka elu. Onye ọrịa ọzọ, T02 (nwoke dị afọ 27), onye nwere myxoid liposarcoma ugboro ugboro n'ụkwụ aka nri mgbe ọ natara ịwa ahụ ise, gosikwara mmeghachi omume akụkụ ahụ ma nwee ihe karịrị otu afọ mgbe ọgwụgwọ gasịrị.
Na 2024, American Society of Clinical Oncology (ASCO) kọrọ napỌmụmụ ihe gbasara TCR-T dị elu (TAEST16001) nke lekwasịrị anya na NY-ESO-1 na sarcoma anụ ahụ dị nro (NCT05549921).
Ụzọ: Nke a bụ ọmụmụ ihe e ji aka mepee emepe, nke nwere otu ogwe aka iji nyochaa irè na nchekwa nke mkpụrụ ndụ TAEST16001 n'ime ndị ọrịa nwere STS dị elu (NCT05549921). Ndị ọrịa debanyere aha natara apheresis, mkpụrụ ndụ T ha dị iche gbasaara na vitro mgbe e mechara mịnye ha site na iji lentiviral vector nke na-egosipụta ike dị elu NY-ESO-1 TCR. Ndị ọrịa natara ọgwụ chemotherapy lymphodepleting ụbọchị atọ (cyclophosphamide 15 mg/kg/ụbọchị na fludarabine 20 mg/m2/ụbọchị). E nyere mkpụrụ ndụ TAEST16001 na 1.2 × 1010± 30% mkpụrụ ndụ (a chọpụtara site na data nkebi nke mbụ anyị) ha natarakwa ọgwụ IL-2 sc ụbọchị iri na anọ. Edobere arụmọrụ ebumnuche (kwa RECIST 1.1) na ọnụego nzaghachi zuru oke (ORR) = 25% maka otu ndị ọrịa iri na abụọ nke ọkwa mbụ.
Nsonaazụ: Ruo Jenụwarị 2024, e debanyere aha ndị ọrịa 8 (M:F 4: 4; nkezi afọ: afọ 40; usoro ọgwụgwọ etiti: 3 (oke: 2-5)). Mkpụrụ ndụ TAEST16001 gosipụtara profaịlụ nchekwa a na-achịkwa nke kwekọrọ na ọmụmụ nkebi nke mbụ gara aga. Ihe omume ọjọọ atọ a na-ahụkarị (n>1) akọpụtara (G) bụ lymphocytopenia (n=8), mbelata ọnụọgụ WBC (n=7), neutropenia (n=6), mmụba γ-GT (n=3), hypokalemia (n=2). Ndị ọrịa isii nwere ọrịa mwepụta cytokine (CRS) (G3: 1; G2: 1; G1: 4), na ndị ọrịa 2 nwetakwara G1 ICANS, ha niile kwụsịrị kpamkpam mgbe a gwọchara ha. Ihe dị mkpa bụ na mgbe nyochachara etuto ahụ abụọ gasịrị, mmadụ 4 egosila na ha nwere akụkụ ụfọdụ, mmadụ 3 nwere ọrịa kwụsiri ike, otu onye nwekwara ọrịa na-aga n'ihu. ORR na ụbọchị njedebe bụ 50%. Oge etiti ruo mgbe a zara ajụjụ mbụ bụ ọnwa 1.1 (1.1 ruo 2.2) ebe oge etiti nzaghachi ahụ bụ ọnwa 5.0 (1.5 ruo 8.8). Ọtụtụ ndị ọrịa ka na-enyocha ya. Mgbe a na-achịkọta data maka otu dose ahụ na nkebi nke mbụ, ORR na dose nke 1.2 × 1010bụ 54.5% (6/11).
Ugbu a, enwere ọtụtụ nnwale ahụike nke teknụzụ ọhụrụ na-egbochi kansa na China na-achọ ndị ọrịa. Maka ndụmọdụ gbasara ọgwụ na teknụzụ ọhụrụ, ị nwere ike ịkpọtụrụ Ngalaba Mba Nile nke Ụlọ Ọgwụ Oncology nke Beijing South Region.
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Ntụaka
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
Oge ozi: Disemba-18-2024