Ucwaningo Olusha Olushicilelwe Ku-Blood: Ukwelashwa Kwe-CD7 CAR-T Okusekelwe Ku-Nanobody kwe-Acute Myeloid Leukemia
Ithimba Lezokwelapha laseLu Daopei lenze intuthuko emangalisayo emkhakheni we-hematology. Ngaphansi kobuholi bukaDkt. Lu Peihua, ucwaningo lwabo oluqavile, "I-Antigen ye-Chimeric ekhethwe ngokwemvelo ye-CD7 esekelwe ku-Nanobody Iseli le-T le-Receptor Ukwelashwa kwe-Acute Myeloid Leukemia”, isanda kushicilelwa kumagazini odumile emhlabeni jikelele Igazi (Isici Somthelela: 21). Lolu cwaningo luqokomisa indlela entsha yokwelapha i-acute myeloid leukemia (AML), ebonisa ukusebenza kahle nokuphepha kokubulala isimila okumangalisayo ngenkathi inikeza ithemba elisha ezigulini ezine-AML ephinde yabuya noma engasabeli kahle (R/R).
Indlela Entsha
Lolu cwaningo luqala ukusetshenziswa kwamaseli e-CD7 CAR-T asekelwe ku-nanobody ekwelashweni kwe-AML. Izindlela zokwelapha zendabuko ze-CAR-T zivame ukusebenzisa izingcezu eziguquguqukayo ze-single-chain (scFv) ezitholakala kuma-antibodies e-monoclonal (mAbs). Lolu cwaningo lusebenzise ama-nanobodies—ama-antibodies e-single-domain atholakala kuma-antibodies e-camelid heavy-chain. Ama-nanobodies, ngenxa yobukhulu bawo obuncane (15kDa uma kuqhathaniswa ne-150kDa human IgG) kanye nokuncipha kwe-immunogenicity, ahlinzeka ngokucaciswa kwe-antigen okuphezulu kanye nokubopha okuqinile ngenkathi kunciphisa imiphumela emibi.
I-NS7CAR-T esekelwe ku-nanobody ibonise ukusebenza kahle kanye nokuphepha okuthuthukisiwe kokulwa nomdlavuza kokubili ezivivinyweni zangaphambi kokwelashwa kanye nezomtholampilo. Imiphumela yangaphambi kokwelashwa iveze ukwanda kwamaseli okuphezulu kanye nomsebenzi wokulwa nomdlavuza uma kuqhathaniswa namaseli e-CAR-T asekelwe ku-scFv. Ngaphezu kwalokho, esivivinyweni somtholampilo seSigaba I, ukwelashwa kufinyelele izinga lokuxolelwa okuphelele elingu-70% phakathi kweziguli eziyi-10 ezine-CD7-positive AML, kanti u-60% ufinyelele isimo esincane sokungaguli kahle kwesifo (MRD).
Umthelela Wezokwelapha
Ucwaningo lubhalise iziguli ezinephrofayili eyingozi kakhulu, okuhlanganisa nalabo ababenokufakelwa amaseli e-hematopoietic stem cell ngaphambili (i-allo-HSCT) noma imigqa eminingi yokwelapha. Naphezu kwalezi zinselele, ukwelashwa kwe-NS7CAR-T okusekelwe ku-nanobody kufinyelele imiphumela ethembisayo ngemiphumela emibi elawulekayo, okuhlanganisa ne-mild cytokine release syndrome (CRS) ku-80% wabahlanganyeli. Azikho izimo zobuthi be-neurotoxic ezibonwe.
Iziqondiso Zesikhathi Esizayo
Lolu cwaningo lugcizelela isidingo sezilingo ezinkulu ukuze kuqinisekiswe ukusebenza kahle nokuphepha kokwelashwa kwe-CD7 CAR-T okusekelwe ku-nanobody ekwelashweni kwe-AML. Luphinde lugqamise izinselele ezifana nokulahlekelwa yi-CD7 antigen, okusalokhu kuyisithiyo esikhulu ezimweni eziphinde zavela. Ukubhekana nalezi zinkinga kuzoba yisihluthulelo sokwenza ngcono ukwelashwa kwezicelo eziningi zezokwelapha.
I-Horizon Entsha Yokwelashwa Kwe-AML
I-AML, isifo esiyinkimbinkimbi kakhulu futhi esingafani segazi, isikhathi eside sidale izinselele ekufinyeleleni ukuphulukiswa okuhlala isikhathi eside kanye nokuthuthukisa amazinga okusinda jikelele. Lokhu okusha okwethulwe yiLu Daopei Medical Team akugcini nje ngokunikeza indlela entsha yokwelapha iziguli kodwa futhi kuqinisa ukuvelela kwazo kwezemfundo ocwaningweni lwegazi lomhlaba wonke.
Lesi sigameko esibalulekile sisebenza njengobufakazi bokuzinikela kwethimba ekuhlanganiseni ucwaningo olusezingeni eliphezulu kanye nokusebenza kwezokwelapha. Njengoba ithimba liqhubeka nokuhlola izindlela zokwelapha ezintsha, umsebenzi wabo uletha ithemba elisha ezigulini emhlabeni wonke futhi uvula indlela yokuthuthuka okuguqulayo ku-hematology.