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Mekhahlelo ea Kalafo
Mekhoa ea Kalafo e Hlahisitsoeng

Kalafo ea CAR-T bakeng sa Myasthenia Gravis (MG)

    Kakaretso

    Myasthenia Gravis (MG) ke lefu le sa foleng la autoimmune neuromuscular le bakoang ke li-autoantibodies (haholo-holo li-anti-acetylcholine receptor antibodies, AchRAb) tse sitisang puisano pakeng tsa methapo le mesifa, e leng se lebisang bofokoling bo feto-fetohang, ptosis, dysphagia, le maemong a tebileng a behang bophelo kotsing ea ho hloleha ho hema. Bakeng sa bakuli ba nang le MG e sa sebetseng ba hlolehang ho sebelisa li-immunosuppressants tse tloaelehileng, IVIG, FcRn inhibitors, le li-complement inhibitors, likhetho tsa kalafo li ntse li lekanyelitsoe.

    Kalafo ea BIOOCUS ea CD19/BCMA CAR-T e nang le sepheo se habeli e emela phekolo e ncha ea lisele tsa autologous e felisang ka nepo lisele tsa B tse bakang pathogenic le lisele tsa plasma tse ikarabellang bakeng sa tlhahiso ea li-autoantibody, e fanang ka monyetla oa pholiso e tebileng le e tšoarellang ho MG e thata ho phekoloa.

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    Kalafo ea CAR-T bakeng sa MG ke eng?

    Kalafo ea CAR-T bakeng sa MG ke kalafo e tsoetseng pele, e etselitsoeng motho ka mong moo lisele tsa T tsa mokuli li entsoeng ka liphatsa tsa lefutso ho hlahisa li-receptor tsa chimeric antigen (CARs) tse shebaneng le CD19 (liseleng tsa B) le BCMA (liseleng tsa plasma). Kamora ho atolosoa laboratoring, lisele tsena tsa CAR-T tse nang le sepheo se habeli li kenngoa hape ho mokuli, moo li khellang ka hloko lisele tsa 'mele tse sebetsang tsa autoreactive tse tsamaisang MG, ka hona li fokotsa maemo a AchRAb le ho tsosolosa ts'ebetso ea methapo ea kutlo.

    Mokhoa ona oa ho sebetsana le sepheo se habeli o sebetsana le likarolo tsa sele le tsa humoral tsa karabelo ea autoimmune, o fana ka ho tsosolosoa ho felletseng ha sesole sa 'mele ha ho bapisoa le mekhoa ea phekolo ea sepheo se le seng kapa ea setso.

    Melemo ea Bohlokoa ea Kalafo ea CAR-T bakeng sa MG

    • Ntlafatso e potlakileng le e tsoelang pele ea matšoao: Phokotso e kgolo mokgatheng wa mesifa, ptosis, diplopia, dysarthria, le bofokodi ba maoto.
    • Ho fokotseha ha lisele tse tebileng tsa B le plasma: Phokotso e tšoailoeng le e tšoarellang ea AchRAb le palo eohle ea B-lymphocyte.
    • Lintlha tse ntlafalitsoeng tsa kliniki: Meputso e meholo ho lintlha tsa Quantitative Myasthenia Gravis (QMG) le Activities of Daily Living (ADL).
    • Profaele e ntle ea polokeho: E mamelleha hantle ntle le ho ba le lefu la ho lokolloa ha cytokine (CRS) kapa chefo ea methapo ea kutlo e bonoang maemong a phekoloang.
    • Ho ka etsahala hore motho a fole nako e telele: E fokotsa kapa e felisa tlhoko ea ho thibela sesole sa 'mele sa nako e telele.
    • E etselitsoe motho ka mong le e nepahetseng: E sebelisa lisele tsa mokuli ka boeena, e fokotsa kotsi ea ho lahloa.

    Mokhoa oa Kalafo

    1. Leukapheresis– Pokello ea lisele tsa T tsa mokuli ka ho sebelisa apheresis ea mali e ka ntle ho tšitiso ea mali.
    2. Boenjiniere ba Liphatsa tsa Lefutso– Lisele tsa T li fetoloa ho hlahisa CD19 le BCMA CARs mme li atolosoa litsing tsa GMP.
    3. Ho lokisa (haeba ho hlokahala)– Ho fokotseha ha lymph ka nako e khutšoanyane ho ntlafatsa ho kenngoa ha CAR-T.
    4. Tšoaetso ea CAR-T– Ho kenngoa ha CD19 CAR-T ka methapong hanngoe (0.5×10⁶/kg) + BCMA CAR-T (1×10⁶/kg).
    5. Tlhokomelo le ho Latela– Tlhahlobo e tloaelehileng ea katoloso ea CAR-T, maemo a AchRAb, lipalo tsa lisele tsa B, lintlha tsa QMG/ADL, le ts'ebetso ea litho ho fihlela likhoeling tse 12+.

    Hobaneng o lokela ho kgetha phekolo ya BIOOCUS's CAR-T bakeng sa MG?

    • Sethala sa CD19/BCMA CAR-T se nang le sepheo se habeli se ntlafalitsoeng ka ho khetheha bakeng sa mafu a autoimmune.
    • Sehlopha sa tlhahiso ea GMP sa maemo a lefats'e le sehlopha se nang le boiphihlelo ba kalafo ea immunotherapy se nang le boiphihlelo maemong a mali a mali le a autoimmune a sa sebetseng hantle.
    • Tšehetso e felletseng ea bakuli ba machaba: ho hokahanya lipuo tse ngata, phetisetso ea boema-fofane, bolulo, le tlhahlobo ea nako e telele.
    • Rekoto e pakiloeng ho CAR-T bakeng sa mafu a autoimmune (ho kenyeletsoa le SLE) le moralo oa kalafo o ikhethileng.
    • Tlhokomelo e felletseng ho tloha tlhahlobong ea pele ho kalafo ho isa tlhokomelong ea kamora ho kenngoa.

    Ntlha-kholo ea Nyeoe ea Thuto ea Mokuli: Mosali ea Lilemo li 20 (LYN) ea nang le Refractory MG

    Semelo sa Mokuli

    • E fumanoe e na le Myasthenia Gravis e sa sebetseng (CNGIIIa, AchRAb-positive) le thymoma/thymic hyperplasia ea mofuta oa B3 kamora ho buuoa.
    • Mafu a mang: osteoporosis, hlooho ea femur ea mahlakore a mabeli le necrosis ea methapo ea mali e ka lehlakoreng le letšehali, anemia ea khaello ea tšepe.
    • Mekhoa e mengata ea phekolo e hlōlehileng (2019–2025): li-steroid tse nang le tekanyo e phahameng + azathioprine → tacrolimus → cyclosporine, IVIG e phetoang khafetsa, efgartigimod, eculizumab + telitacicept, le rituximab (500 mg, ha e sebetse hantle).

    Kalafo ea CAR-T

    • Pudungwana 2025: Protokhole ya CAR-T e qadile; cyclosporine e emisitsoe.
    • La 1 Tšitoe 2025: Pokello ea lisele tsa mali tsa mononuclear tse ka ntle ho naha.
    • La 15 Tšitoe 2025: Tšehetso ea CD19 CAR-T (0.5×10⁶/kg) + BCMA CAR-T (1×10⁶/kg).
    • Ha ho liketsahalo tse mpe ho bonoa kamora ho kenngoa.

    Liphetho tsa Kamora Kalafo (ho tloha ka Hlakubele 2026)

    • Katoloso ea CAR-T: Katoloso e potlakileng ea 'mele ka har'a 'mele ka CD19 CAR-T e phahameng ho D10 (7.62%, 4.622×10⁷/L) le BCMA CAR-T ho D10 (17.17%, 1.0414×10⁸/L); ho fumanoa ho tšoarellang ho fihlela Khoeling ea 3.
    • Ntlafatso ea Laboratori:
    • Phokotso e kholo maemong a AchRAb le palo yohle ya B-lymphocyte.
    • Palo e tsitsitseng ea mali, ts'ebetso ea sebete le liphio.
    • Maemo a immunoglobulin a hlokometsoe (liphetoho tsa nakoana li lebelletsoe ka lebaka la ho fokotseha ha lisele tsa B).
      • Lintlha tsa Bongaka: Ntlafatso e bonahalang lintlheng tsa QMG le ADL, e bonts'ang ho fokotseha ha bofokoli ba mesifa le ts'ebetso e ntlafetseng ea letsatsi le letsatsi.
      • Phomolo ea Matšoao: Phetoho e bonahalang kapa ntlafatso e bonahalang ho diplopia, ho thatafala ha sefahleho, dysarthria, le mokhathala oa maoto le matsoho.

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