Kev Kho Mob CAR-T: Lub Neej Yav Tom Ntej Zoo Rau Cov Kab Mob T-Cell Malignancies
Kev kho mob Chimeric Antigen Receptor T-cell (CAR-T) tau hloov pauv txoj kev kho mob ntawm cov kab mob B-cell malignancies, muab kev zam txim ntev thiab txawm tias kho tau rau ntau tus neeg mob. Txhawb nqa los ntawm cov kev vam meej no, cov kws tshawb fawb tau tig lawv lub hom phiaj mus rau kev siv CAR-T rau cov kab mob T-cell, suav nrog T-Cell Lymphomas (TCL) thiab T-cell mob qog ntshav lymphoblastic leukemia (T-ALL). Txawm li cas los xij, cov mob qog ntshav T-cell no muaj ntau yam teeb meem rau kev tsim kho CAR-T.
Cov kab mob qog nqaij hlav T-cell, uas yog ib feem tseem ceeb ntawm cov menyuam yaus thiab cov neeg laus, paub txog lawv txoj kev ua siab tawv thiab kev tiv thaiv cov kev kho mob ib txwm muaj. T-ALL thiab TCL muaj ntau yam sib txawv, nrog rau cov txiaj ntsig tsis zoo hauv cov chaw rov qab los lossis tsis kho (r/r), qhia txog qhov xav tau kev kho mob tshiab sai. Kev kho CAR-T rau cov kab mob qog nqaij hlav T-cell tau txais kev saib xyuas tseem ceeb vim nws muaj peev xwm los muab kev daws teeb meem zoo thiab muaj txiaj ntsig.
Qhov teeb meem yog nyob rau hauv kev sib koom ua ke ntawm cov hom phiaj antigen ntawm cov T-cells phem thiab cov T-cells ib txwm muaj, uas tuaj yeem ua rau "fratricide," qhov twg CAR-T cells tsis txhob txwm rhuav tshem cov T-cells noj qab haus huv. Tsis tas li ntawd, T-cell aplasia, uas tuaj yeem ua rau cov neeg mob tsis muaj zog rau kev kis kab mob, ua rau muaj kev pheej hmoo loj dua. Txawm hais tias muaj cov teeb meem no, kev nce qib hauv kev kho mob tsis ntev los no tau ua pov thawj cov txiaj ntsig zoo rau CAR-T hauv T-ALL thiab TCL.
Ib qho kev tshuaj xyuas tsis ntev los no tau luam tawm hauv Kev Nce Qib Ntshav qhia txog ntau qhov kev sim tshuaj kho mob zoo. Ib txoj hauv kev suav nrog kev tsom mus rau CD7, ib qho protein uas qhia tawm ntawm qhov chaw ntawm T-ALL thiab qee cov T-cell lymphomas. Hauv kev sim theem thaum ntxov, CD7-targeted CAR-T kev kho mob tau pom tias muaj txiaj ntsig zoo, ua tiav kev zam txim tag nrho rau ntau tus neeg mob. Tsis tas li ntawd, cov tswv yim tsom mus rau kev txo qis "fratricide" thiab txhim kho kev tsim cov CAR-T cell tab tom ua rau muaj kev tshawb fawb tshiab hauv kev kho mob.
Cov kev sim tsis ntev los no kuj tau sim kho cov T-cell kom txhim kho qhov tshwj xeeb thiab kev ruaj khov ntawm CAR-T cell. Piv txwv li, kev siv CRISPR-Cas9 thev naus laus zis los tsom mus rau cov antigens tshwj xeeb xws li CD5, CD7, thiab TRBC tau pom tias muaj peev xwm txhim kho kev nyab xeeb thiab kev ua haujlwm zoo. Cov txiaj ntsig thaum ntxov qhia tau tias CAR-T kev kho mob, thaum tsim kho kom zoo, tuaj yeem dhau los ua riam phom muaj zog tiv thaiv T-cell malignancies.
Ntxiv mus, kev sib txuas CAR-T kev kho mob nrog lwm yam kev kho mob, xws li allogeneic hematopoietic stem cell transplantation (allo-HSCT), tau pom tias muaj kev cia siab rau kev ua kom muaj sia nyob ntev dua thiab tiv thaiv kev rov qab mob dua. Hauv theem II kev sim ntawm CD7-targeted CAR-T kev kho mob, 63.5% ntawm cov neeg mob tseem nyob hauv kev zam txim tom qab ob xyoos, nrog rau cov neeg tau txais allo-HSCT muaj kev ciaj sia nyob zoo dua qub (PFS).
Thaum kev tshawb fawb nce qib, qhov kev cia siab rau kev kho mob CAR-T hauv cov kab mob T-cell zoo li muaj kev cia siab ntau ntxiv. Txawm hais tias tseem muaj cov teeb meem loj heev uas yuav tsum kov yeej, suav nrog kev tswj hwm cov kab mob cytokine release syndrome (CRS) thiab neurotoxicity, kev nkag siab txog CAR-T thev naus laus zis txuas ntxiv nthuav dav nws cov kev siv.
Ntawm BIOOCUS, peb cog lus tias yuav nyob rau pem hauv ntej ntawm kev tsim kho CAR-T thiab zoo siab los muab kev kho mob tshiab no rau cov neeg mob thoob ntiaj teb. Raws li kev sim tshuaj kho mob txuas ntxiv mus, peb tseem muaj kev cia siab tias kev kho mob CAR-T yuav muaj ib hnub muab kev xaiv kho rau cov neeg uas raug kev txom nyem los ntawm T-cell malignancies, coj kev cia siab tshiab rau cov neeg mob thiab tsev neeg uas xav tau kev kho mob zoo.
Yog xav paub ntxiv txog peb cov kev pab kho mob CAR-T, mus saib peb lub vev xaib lossis tiv tauj peb pab neeg txhawb nqa cov neeg mob.