Chithandizo cha CAR-T: Tsogolo Lodalirika la Matenda a T-Cell

Chithandizo cha Chimeric Antigen Receptor T-cell (CAR-T) chasintha kwambiri chithandizo cha khansa ya B-cell, kupereka machiritso okhalitsa komanso machiritso kwa odwala ambiri. Atalimbikitsidwa ndi kupambana kumeneku, ofufuza ayang'ana kwambiri pakugwiritsa ntchito CAR-T pa khansa ya T-cell, kuphatikizapo T-Cell Lymphomas (TCL) ndi T-cell acute lymphoblastic leukemia (T-ALL). Komabe, khansa ya T-cell iyi imabweretsa mavuto apadera pakukula kwa chithandizo cha CAR-T.

Matenda a khansa a T-cell, omwe ndi gawo lalikulu la khansa ya ana ndi akuluakulu, amadziwika kuti ndi amphamvu komanso osalandira chithandizo chamankhwala chochiritsira. Matenda a T-ALL ndi TCL ndi osiyana kwambiri, ndipo zotsatira zake zimakhala zoipa m'malo omwe amabwereranso kapena osachiritsika (r/r), zomwe zikusonyeza kufunika kwa njira zatsopano zochiritsira. Chithandizo cha CAR-T cha khansa ya T-cell chakopa chidwi chachikulu chifukwa cha kuthekera kwake kupereka yankho lolunjika komanso lothandiza.

Vuto lili pa kuwonetsedwa kwa ma antigen pakati pa maselo a T oopsa ndi maselo a T abwinobwino, zomwe zingayambitse "fratricide," komwe maselo a CAR-T amawononga maselo a T athanzi mwangozi. Kuphatikiza apo, T-cell aplasia, yomwe ingapangitse odwala kukhala pachiwopsezo cha matenda, imabweretsa chiopsezo china chachikulu. Ngakhale kuti pali zopinga izi, kupita patsogolo kwaposachedwa kwachipatala kwawonetsa zotsatira zabwino za CAR-T mu T-ALL ndi TCL.

Ndemanga yaposachedwa yofalitsidwa mu Kupita Patsogolo kwa Magazi Ikuwonetsa mayeso angapo azachipatala odalirika. Njira imodzi ikuphatikizapo kuyang'ana CD7, puloteni yomwe imaonekera pamwamba pa T-ALL ndi ma lymphoma ena a T-cell. M'mayesero oyambirira, mankhwala a CAR-T omwe amawunikira CD7 awonetsa kugwira ntchito bwino kwambiri, zomwe zathandiza odwala ambiri kuchira kwathunthu. Kuphatikiza apo, njira zochepetsera "fratricide" ndikupititsa patsogolo kupanga maselo a CAR-T zikutsegulira njira yopita patsogolo kuchipatala.

Mayeso aposachedwapa ayesanso kusintha maselo a T kuti awonjezere kukhazikika kwa maselo a CAR-T. Mwachitsanzo, kugwiritsa ntchito ukadaulo wa CRISPR-Cas9 polimbana ndi ma antigen enaake monga CD5, CD7, ndi TRBC kwawonetsa kuthekera kokweza chitetezo ndi magwiridwe antchito. Zotsatira zoyambirira zikusonyeza kuti chithandizo cha CAR-T, chikapangidwa mosamala, chingakhale chida champhamvu cholimbana ndi khansa ya T-cell.

Kuphatikiza apo, kuphatikiza chithandizo cha CAR-T ndi mankhwala ena, monga allogeneic hematopoietic hematopoietic stem cell transplantation (allo-HSCT), kwawonetsa chiyembekezo pakuwonjezera kupulumuka ndikuletsa kubwereranso. Mu mayeso a gawo lachiwiri la chithandizo cha CAR-T choyang'aniridwa ndi CD7, 63.5% ya odwala adakhalabe omasuka patatha zaka ziwiri, ndipo omwe adalandira allo-HSCT adakhala ndi moyo wabwino kwambiri wopanda progression-free survival (PFS).

Pamene kafukufuku akupita patsogolo, malo ochiritsira CAR-T mu khansa ya T-cell akuwoneka kuti ali ndi chiyembekezo. Ngakhale kuti pali mavuto akuluakulu oti athetsedwe, kuphatikizapo kuthana ndi vuto lalikulu la kutulutsidwa kwa cytokine (CRS) ndi poizoni wa mitsempha, kumvetsetsa komwe kukuchitika kwa ukadaulo wa CAR-T kukupitilizabe kukulitsa ntchito zake zomwe zingatheke.

Ku BIOOCUS, tadzipereka kukhala patsogolo pa chitukuko cha chithandizo cha CAR-T ndipo tikusangalala kupereka chithandizo chamakonochi kwa odwala padziko lonse lapansi. Pamene mayeso azachipatala akupitilizabe kusintha, tikukhulupirira kuti chithandizo cha CAR-T tsiku lina chidzapereka njira yochiritsira kwa omwe akudwala khansa ya T-cell, ndikubweretsa chiyembekezo chatsopano kwa odwala ndi mabanja omwe akufunika njira zochizira zogwira mtima.

Kuti mudziwe zambiri zokhudza mapulogalamu athu ochizira matenda a CAR-T, pitani patsamba lathu kapena funsani gulu lathu lothandizira odwala.