Kafukufuku Wotsogola Wofalitsidwa mu Blood: Nanobody-Based CD7 CAR-T Therapy for Acute Myeloid Leukemia
Gulu la Zachipatala la Lu Daopei lapita patsogolo kwambiri pankhani ya magazi. Motsogozedwa ndi Dr. Lu Peihua, kafukufuku wawo wodziwika bwino, "Antigen ya Chimeric Yosankhidwa Mwachibadwa ya CD7 Yochokera ku Nanobody Selo ya T yolandirira "Chithandizo cha Khansa ya Myeloid", posachedwapa yafalitsidwa mu magazini yotchuka padziko lonse lapansi Magazi (Chinthu Chokhudza Zotsatira: 21). Kafukufukuyu akuwonetsa njira yatsopano yochizira khansa ya m'magazi ya myeloid (AML), yomwe ikuwonetsa mphamvu komanso chitetezo chapadera chopha chotupa komanso kupereka chiyembekezo chatsopano kwa odwala omwe ali ndi AML yobwereranso kapena yosagwira ntchito (R/R).
Njira Yatsopano
Kafukufukuyu ndiye amene anayambitsa kugwiritsa ntchito maselo a CD7 CAR-T okhala ndi nanobody mu chithandizo cha AML. Mankhwala achikhalidwe a CAR-T nthawi zambiri amagwiritsa ntchito zidutswa zosinthika za single-chain (scFv) zochokera ku ma antibodies a monoclonal (mAbs). Kafukufukuyu adagwiritsa ntchito ma nanobodies—ma antibodies a single-domain ochokera ku ma antibodies a camelid heavy-chain. Ma nanobodies, chifukwa cha kukula kwawo kochepa (15kDa poyerekeza ndi 150kDa human IgG) komanso kuchepa kwa chitetezo chamthupi, amapereka antigen yabwino kwambiri komanso kugwirizana kogwirizana pamene akuchepetsa zotsatirapo zake.
NS7CAR-T yochokera ku nanobody inasonyeza kuti imagwira ntchito bwino komanso kuti itetezeke polimbana ndi chotupa m'mayesero asanayambe kuchipatala komanso azachipatala. Zotsatira za kafukufukuyu zinawonetsa kuchuluka kwa maselo ndi ntchito yolimbana ndi chotupa poyerekeza ndi maselo a CAR-T omwe ali ndi scFv. Kuphatikiza apo, mu kafukufuku wachipatala wa Gawo Loyamba, chithandizochi chinapeza chiwopsezo cha 70% cha odwala 10 omwe ali ndi CD7-positive AML, ndipo 60% adapeza kuti palibe matenda otsala (MRD) omwe ali ndi vuto lililonse.
Zotsatira Zachipatala
Kafukufukuyu adalemba odwala omwe ali ndi mbiri yowopsa kwambiri, kuphatikizapo omwe adasinthidwa kale maselo oyambira a hematopoietic (allo-HSCT) kapena mitundu ingapo ya chithandizo. Ngakhale kuti panali zovuta izi, chithandizo cha NS7CAR-T chochokera ku nanobody chidapeza zotsatira zabwino zomwe zidapangitsa kuti pakhale zotsatirapo zoyipa, kuphatikizapo mild cytokine release syndrome (CRS) mwa 80% ya omwe adachita nawo kafukufukuyu. Palibe milandu ya neurotoxicity yomwe idawonedwa.
Malangizo a M'tsogolo
Kafukufukuyu akugogomezera kufunika kwa mayeso akuluakulu kuti atsimikizire bwino momwe chithandizo cha CD7 CAR-T chochokera ku nanobody chimagwirira ntchito komanso chitetezo chake pa chithandizo cha AML. Ikuwonetsanso zovuta monga kutayika kwa ma antigen a CD7, komwe kumakhalabe vuto lalikulu kwa odwala omwe abwereranso m'matenda. Kuthetsa mavutowa kudzakhala kofunikira kwambiri pakukonza bwino chithandizochi kuti chigwiritsidwe ntchito bwino kuchipatala.
Chiyembekezo Chatsopano cha Chithandizo cha AML
AML, khansa ya m'magazi yovuta kwambiri komanso yosiyana, yakhala ikupereka mavuto kwa nthawi yayitali pakuchepetsa kukalamba kwa maselo ndikuwongolera kuchuluka kwa anthu omwe apulumuka. Kapangidwe katsopano kameneka kamene kanakhazikitsidwa ndi Lu Daopei Medical Team sikuti kamangopereka njira yatsopano yochiritsira odwala komanso kumalimbitsa kutchuka kwawo pamaphunziro mu kafukufuku wapadziko lonse wa hematology.
Chochitika chachikuluchi chikutsimikizira kudzipereka kwa gululi pogwirizanitsa kafukufuku wamakono komanso machitidwe azachipatala. Pamene gululi likupitiliza kufufuza njira zatsopano zochiritsira, ntchito yawo imabweretsa chiyembekezo chatsopano kwa odwala padziko lonse lapansi ndipo ikutsegulira njira yosinthira njira mu hematology.