Kev Kov Yeej Cov Kev Cov nyom hauv Kev Kho Mob CAR-T rau Cov Mob Cancer Ntshav T-Cell
Kev kho mob Chimeric Antigen Receptor T-cell (CAR-T) tau ua pov thawj tias yog kev kho mob tshiab rau cov kab mob ntshav uas tau los ntawm B-cell, muab kev ua haujlwm zoo thiab kev nyab xeeb. Txawm li cas los xij, nws daim ntawv thov rau cov kab mob T-cell, xws li T-cell mob qog ntshav lymphoblastic (T-ALL) thiab cov kab mob peripheral. T-Cell Lymphoma (PTCL), muaj ntau yam teeb meem loj heev. Ib qho teeb meem tseem ceeb yog qhov zoo sib xws ntawm cov T-cells phem thiab cov T-cells ib txwm muaj, ua rau nws nyuaj rau tsuas yog tsom mus rau cov hlwb qog nqaij hlav xwb yam tsis ua rau cov T-cells noj qab nyob zoo puas tsuaj. Qhov no ua rau muaj qhov xwm txheej hu ua "fratricide," qhov twg cov hlwb CAR-T tawm tsam ob qho tib si cov hlwb qog nqaij hlav thiab cov hlwb T ib txwm muaj, ua rau kev kho mob tsis zoo. Ntxiv mus, qhov sib txawv ntawm cov T-cell malignancies ua rau kev txheeb xyuas cov hom phiaj ntawm CAR-T cell thoob ntiaj teb nyuaj, vim tias ib qho antigen yuav tsis qhia tawm thoob plaws txhua lub hlwb qog nqaij hlav.
Hauv kev sim tshuaj, CAR-T hlwb uas tsom mus rau pan-T antigens xws li CD5 thiab CD7 tau pom qee qhov kev vam meej hauv kev kho mob T-cell malignancies. Cov hom phiaj no pom muaj nyob rau ntawm qhov chaw ntawm feem ntau T-cell malignancies, tab sis lawv kuj tshwm sim ntawm T-cell ib txwm muaj, ua rau muaj cov kev mob tshwm sim loj xws li T-cell depletion, kev tiv thaiv kab mob tsis zoo, thiab kev kis kab mob ntau ntxiv. Txhawm rau kom txo tau cov teeb meem no, cov kws tshawb fawb tab tom tsom mus rau cov "txwv" T-cell antigens tshwj xeeb, xws li CD4, CD30, CD37, thiab CCR4. Cov antigens no xaiv ntau dua rau qee pawg ntawm T-cells, uas tuaj yeem txo qhov kev pheej hmoo ntawm fratricide thiab khaws cia kev ua haujlwm ntawm lub cev tiv thaiv kab mob ib txwm muaj. Txawm li cas los xij, kev tshawb fawb txog cov antigens txwv no tseem nyob rau theem thaum ntxov, thiab kev xaiv tus neeg mob kom zoo yog qhov tseem ceeb los txiav txim siab lub hom phiaj tsim nyog tshaj plaws rau txhua rooj plaub.
Lwm txoj kev tshawb nrhiav yog kev tsim cov hlwb CAR-T allogeneic, uas yog los ntawm cov neeg pub dawb noj qab haus huv es tsis yog cov neeg mob lawv tus kheej. Cov hlwb CAR-T allogeneic tuaj yeem raug hloov kho kom tiv thaiv kev kis tus kab mob qog nqaij hlav thiab txo qhov kev pheej hmoo ntawm tus kab mob graft-versus-host (GvHD), uas yog ib qho teeb meem tshwm sim hauv kev hloov pauv. Txawm li cas los xij, cov hlwb no ntsib teeb meem xws li kev tsis lees txais lub cev tiv thaiv kab mob, uas tuaj yeem txwv lawv txoj kev ua haujlwm mus sij hawm ntev. Txhawm rau daws qhov teeb meem no, cov txheej txheem hloov kho noob caj noob ces xws li CRISPR / Cas9 thiab kev hloov kho hauv paus tab tom raug tshawb nrhiav los hloov kho cov hlwb CAR-T, ua rau lawv siv tau thoob ntiaj teb thiab muaj kev nyab xeeb dua rau cov neeg mob. Kev hloov kho hauv paus, tshwj xeeb, muab lwm txoj hauv kev zoo rau kev hloov kho noob caj noob ces ib txwm muaj, vim nws zam kev pheej hmoo cuam tshuam nrog kev tawg DNA ob txoj hlua, txo cov tshuaj lom hauv noob caj noob ces thiab txhim kho qhov kev nyab xeeb ntawm kev kho mob CAR-T.
Txawm hais tias muaj cov kev nce qib no los xij, tseem muaj ntau yam teeb meem uas tseem muaj. Cov qe ntshav CAR-T feem ntau tsis tuaj yeem nyob ntev hauv lub cev, uas tuaj yeem ua rau tus kab mob rov qab los. Tom qab kho nrog CD7-targeted CAR-T cell, piv txwv li, CD7-negative T-cells tuaj yeem tshwm sim thiab tiv taus CAR-T cell tua, ua rau kev kho mob nyuaj dua. Cov kws tshawb fawb tab tom tshawb nrhiav txoj hauv kev los txhim kho lub neej ntev thiab kev ua haujlwm ntawm CAR-T cell, suav nrog kev sib txuas CAR-T therapy nrog lwm yam kev kho mob, xws li stem cell transplants, los sib sau ua ke thiab tswj kev zam txim. Txoj hauv kev no, hu ua "bridging therapy," tuaj yeem muab ib txheej ntxiv ntawm kev tiv thaiv tiv thaiv kev rov qab los, tshwj xeeb tshaj yog rau cov neeg mob uas muaj mob qog nqaij hlav ntau.
Cov teeb meem tom qab kev kho mob CAR-T, suav nrog cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), thiab opportunistic infections, kuj yog qhov txhawj xeeb. Kev txo qis T-cell, tshwj xeeb, ua rau cov neeg mob muaj kev pheej hmoo rau kev rov ua dua ntawm cov kab mob latent xws li Epstein-Barr virus (EBV) thiab cytomegalovirus (CMV), thaum kev txwv cov pob txha tuaj yeem ua rau cytopenia ntev. Txhawm rau txo cov kev pheej hmoo no, cov kws tshawb fawb tab tom tshawb nrhiav txoj hauv kev los txhim kho kev nyab xeeb thiab kev ua haujlwm ntawm CAR-T cell, xws li kev qhia txog kev hloov pauv kev nyab xeeb thiab siv cov txheej txheem kho mob luv luv kom txo cov kev mob tshwm sim.
Zuag qhia tag nrho, thaum CAR-T kev kho mob tau ua tiav zoo hauv kev kho mob qog ntshav T-cell, cov teeb meem ntsig txog kev tsom mus rau antigen, teeb meem ntawm lub cev tiv thaiv kab mob, thiab kev ua mus ntev tseem muaj. Kev tshawb fawb thiab kev tsim kho tshiab hauv CAR-T thev naus laus zis, suav nrog kev tsim cov kev kho mob dual-target, cov txheej txheem kho gene, thiab kev xaiv cov neeg mob kom meej dua, yog qhov tseem ceeb rau kev qhib lub peev xwm kawg ntawm CAR-T kev kho mob hauv kev kho mob qog ntshav T-cell. Raws li kev sim tshuaj kho mob txuas ntxiv tshawb nrhiav cov tswv yim tshiab, kev cia siab yog tias CAR-T kev kho mob yuav hloov pauv los muab cov kev xaiv kho mob ruaj khov thiab muaj kev nyab xeeb dua rau cov neeg mob uas muaj cov qog ntshav nyuaj no.