Chidzidzo Chekubudirira Chakabudiswa muRopa: Nanobody-Based CD7 CAR-T Therapy yeAcute Myeloid Leukemia
Chikwata cheLu Daopei Medical Team chafambira mberi zvikuru munyaya dzeropa. Vachitungamirirwa naDr. Lu Peihua, chidzidzo chavo chakatanga, "Antigen yeCD7-Targeted Chimeric Yakasarudzwa Nemuviri Yese muNanobody" Sero reReceptor T "Kurapa kweAcute Myeloid Leukemia", yakaburitswa munguva pfupi yapfuura mumagazini inozivikanwa pasi rose Ropa (Chinhu Chinokonzera Kurwara: 21). Tsvakurudzo iyi inoratidza nzira itsva yekurapa chirwere cheAcute myeloid leukemia (AML), ichiratidza kushanda zvakanaka uye kuchengetedzeka kwechirwere ichi uku ichipa tariro itsva kune varwere vane chirwere cheAML chinodzokera shure kana chisingadzoreki (R/R).
Maitiro Ekuvandudza
Chidzidzo ichi chakatanga kushandiswa kwemasero eCD7 CAR-T ane nanobody mukurapa kweAML. Kurapa kweCAR-T kwechinyakare kunowanzo shandisa zvikamu zve single-chain variable (scFv) zvinobva kuma monoclonal antibodies (mAbs). Tsvakurudzo iyi yakashandisa nanobodies—single-domain antibodies inobva kuma camelid heavy-chain antibodies. Nanobodies, nekuda kwehukuru hwavo hudiki (15kDa zvichienzaniswa ne150kDa human IgG) uye kudzikira kwe immunogenicity, inopa antigen specificity yepamusoro uye kubatana uku ichideredza migumisiro yakaipa.
NS7CAR-T yakagadzirwa ne nanobody yakaratidza kushanda zvakanaka uye kuchengetedzeka kwekudzivirira bundu mumiedzo yepamberi pekiriniki neyekiriniki. Mhedzisiro yepamberi pekiriniki yakaratidza kuwanda kwemasero uye kushanda kwekudzivirira bundu zvichienzaniswa nemasero eCAR-T akavakirwa pa scFv. Uyezve, muyedzo yekiriniki yePhase I, kurapwa kwakawana chiyero chekuregererwa kwakakwana kwe70% pakati pevarwere gumi vane CD7-positive AML, uye 60% yakawana mamiriro mashoma ekusara kwechirwere (MRD)-negative.
Mhedzisiro yeKliniki
Muedzo uyu wakanyoresa varwere vane njodzi huru, kusanganisira avo vakamboiswa masero eropa (allo-HSCT) kana kuti vakamborapwa nenzira dzakasiyana-siyana. Pasinei nematambudziko aya, mushonga weNS7CAR-T wakagadzirwa nemuviri wakawana mhedzisiro yakanaka ine migumisiro inogoneka, kusanganisira mild cytokine release syndrome (CRS) mu80% yevatori vechikamu. Hapana nyaya dzekuti vane chepfu muuropi dzakaonekwa.
Mirayiridzo Yeramangwana
Chidzidzo ichi chinosimbisa kudiwa kwemiedzo mikuru kuti isimbise kushanda uye kuchengetedzeka kwekurapa kweCD7 CAR-T kwakavakirwa pa nanobody mukurapa kweAML. Chinosimbisawo matambudziko akadai sekurasikirwa neCD7 antigen, iyo ichiri chipingamupinyi chikuru muzviitiko zvekudzokera shure. Kugadzirisa matambudziko aya kuchave chinhu chakakosha pakuvandudza kurapwa kwemishonga iyi kuti ishandiswe mukurapa kwakakura.
Nzira Itsva Yekurapwa kweAML
AML, chirwere chegomarara reropa chakaoma uye chakasiyana-siyana, chagara chichikonzera matambudziko mukuwana zororo rinogara kwenguva refu uye kuvandudza huwandu hwevanhu vanorarama. Hutsva uhu hwakatangwa neLu Daopei Medical Team hahungopi nzira itsva yekurapa varwere chete asiwo hunosimbisa mukurumbira wavo muzvidzidzo mukutsvagisa kweropa pasi rose.
Chiitiko ichi chinoratidza kuzvipira kwechikwata ichi mukubatanidza tsvakurudzo yepamusoro uye maitiro ekurapa. Sezvo chikwata ichi chichienderera mberi nekutsvaga nzira dzekurapa dzinochinja-chinja, basa ravo rinounza tariro itsva kuvarwere pasi rese uye rinovhura nzira yekufambira mberi mukurapa kweropa.