Chithandizo cha CAR-T cha Myasthenia Gravis (MG)

Myasthenia Gravis (MG) ndi matenda osatha a autoimmune neuromuscular omwe amayamba chifukwa cha ma autoantibodies (makamaka ma anti-acetylcholine receptor antibodies, AchRAb) omwe amasokoneza kulumikizana pakati pa mitsempha ndi minofu, zomwe zimapangitsa kuti kufooka kusinthasintha, ptosis, dysphagia, komanso nthawi zina kupuma movutikira komwe kungawononge moyo. Kwa odwala omwe ali ndi MG yokana yomwe imalephera kulandira ma immunosuppressants wamba, IVIG, FcRn inhibitors, ndi ma complement inhibitors, njira zochiritsira zimakhala zochepa.

Chithandizo cha BIOOCUS cha CD19/BCMA CAR-T chokhala ndi zolinga ziwiri chikuyimira chithandizo chapamwamba cha maselo a autologous chomwe chimachotsa maselo a B omwe ali ndi matenda ndi maselo a plasma omwe amachititsa kupanga ma antibodies a autoimmune, zomwe zimapangitsa kuti pakhale kuchira kwakukulu komanso kolimba mu MG yovuta kuchiza.

Chithandizo cha CAR-T cha MG ndi chithandizo chapamwamba komanso chopangidwa mwapadera chomwe maselo a T a wodwala amapangidwa mwa majini kuti azitha kutulutsa ma receptor a chimeric antigen (CARs) omwe amalunjika ku CD19 (pa maselo a B) ndi BCMA (pa maselo a plasma). Pambuyo pokulitsa mu labotale, maselo a CAR-T awa omwe ali ndi zolinga ziwiri amabwereranso mwa wodwalayo, komwe amachotsa maselo oteteza thupi omwe amayendetsa MG, potero amachepetsa kuchuluka kwa AchRAb ndikubwezeretsa ntchito ya mitsempha yamagazi.

Njira yogwiritsira ntchito njira ziwiri iyi imayang'ana mbali zonse ziwiri za maselo ndi za humoral zomwe zimayambitsa chitetezo chamthupi, zomwe zimapangitsa kuti chitetezo chamthupi chikhazikike bwino poyerekeza ndi njira zochiritsira za single-target kapena zachikhalidwe.

• Kupita patsogolo kwa zizindikiro mwachangu komanso mosalekeza: Kuchepetsa kwambiri kutopa kwa minofu, ptosis, diplopia, dysarthria, ndi kufooka kwa miyendo.
• Kuchepa kwa maselo a B-deep ndi plasma-cell: Kuchepa kodziwika bwino komanso kosatha kwa AchRAb ndi chiwerengero chonse cha B-lymphocyte.
• Ziwerengero zabwino zachipatala: Kupambana kwakukulu mu zigoli za Quantitative Myasthenia Gravis (QMG) ndi Activities of Daily Living (ADL).
• Mbiri yabwino yachitetezo: Yolekerera bwino popanda cytokine release syndrome (CRS) kapena neurotoxicity yomwe imapezeka m'matenda omwe achiritsidwa.
• Kuthekera kwa kuchira kwa nthawi yayitali: Amachepetsa kapena kuthetsa kufunikira kwa chitetezo chamthupi chosatha.
• Zopangidwira munthu payekha komanso zolondola: Amagwiritsa ntchito maselo a wodwalayo, kuchepetsa chiopsezo chokana.

1. Leukapheresis- Kusonkhanitsa maselo a T a wodwalayo kudzera mu apheresis ya magazi.
2. Uinjiniya wa Majini- Ma cell a T amasinthidwa kuti apereke ma CD19 ndi ma BCMA CAR ndipo amakulitsidwa m'malo opangira GMP.
3. Kukonza (ngati pakufunika)- Kuchepa kwa lymphodepletion kwakanthawi kuti CAR-T engraftment ikhale yabwino.
4. Kulowetsedwa kwa CAR-T– Kulowetsedwa kamodzi kokha kwa CD19 CAR-T (0.5×10⁶/kg) + BCMA CAR-T (1×10⁶/kg).
5. Kuyang'anira ndi Kutsatira- Kuwunika pafupipafupi kukula kwa CAR-T, kuchuluka kwa AchRAb, kuchuluka kwa maselo a B, kuchuluka kwa QMG/ADL, ndi kugwira ntchito kwa ziwalo kwa miyezi 12+.

• Pulatifomu yapamwamba kwambiri ya CD19/BCMA CAR-T yokhala ndi zolinga ziwiri yokonzedwa bwino kwambiri pochiza matenda odziteteza ku matenda a autoimmune.
• Gulu la akatswiri opanga GMP padziko lonse lapansi komanso gulu lodziwa bwino ntchito yothandiza anthu odwala matenda a immunotherapy lomwe lili ndi luso pa matenda a khansa ya m'magazi komanso matenda a autoimmune omwe sagwira ntchito bwino.
• Chithandizo chokwanira cha odwala padziko lonse lapansi: kulumikizana kwa zilankhulo zosiyanasiyana, kusamutsa odwala kupita ku eyapoti, malo ogona, ndi kutsatira odwala kwa nthawi yayitali.
• Mbiri yotsimikizika mu CAR-T ya matenda a autoimmune (kuphatikizapo SLE) ndi kukonzekera chithandizo chapadera.
• Chisamaliro chathunthu kuyambira kuwunika asanayambe chithandizo mpaka kuyang'anira pambuyo pa kulowetsedwa.