CAR-T (Chimeric Antigen Receptor T-cell) yog dab tsi?
Ua ntej, cia peb saib ntawm tib neeg lub cev tiv thaiv kab mob.
Lub cev tiv thaiv kab mob yog tsim los ntawm kev sib txuas ntawm cov hlwb, cov ntaub so ntswg, thiab cov kabmob uas ua haujlwm ua ketiv thaiv lub cev.Ib qho ntawm cov hlwb tseem ceeb koom nrog yog cov qe ntshav dawb, tseem hu ua leukocytes,uas tuaj nyob rau hauv ob hom yooj yim uas ua ke los nrhiav thiab rhuav tshem cov kab mob uas ua rau muaj kab mob los yogtshuaj.
Qhov thib ob hom ntawm leukocytes yog:
Phagocytes, cov hlwb uas zom cov kab mob nkag mus.
Lymphocytes, cov hlwb uas tso cai rau lub cev kom nco qab thiab paub txog yav dhau los invaders thiab pablub cev rhuav tshem lawv.
Ib tug xov tooj ntawm cov hlwb sib txawv yog suav tias yog phagocytes.Feem ntau hom yog neutrophil,uas feem ntau tua cov kab mob.Yog tias kws kho mob txhawj xeeb txog kev kis kab mob, lawv yuav xajkuaj ntshav kom pom tias tus neeg mob puas muaj cov neutrophils ntau ntxiv uas tshwm sim los ntawm tus kab mob.
Lwm hom phagocytes muaj lawv tus kheej txoj haujlwm kom paub tseeb tias lub cev teb tau zoomus rau ib hom invader tshwj xeeb.
Ob hom lymphocytes yog B lymphocytes thiab T lymphocytes.Lymphocytes pib tawmnyob rau hauv cov pob txha pob txha thiab txawm nyob ntawd thiab loj hlob mus rau hauv B hlwb, los yog lawv tawm mus rau thymuscaj pas, qhov uas lawv loj hlob rau hauv T cell.B lymphocytes thiab T lymphocytes muaj caisKev ua haujlwm: B lymphocytes zoo li lub cev cov tub rog kev txawj ntse, nrhiav tawm lawvlub hom phiaj thiab xa kev tiv thaiv los xauv rau lawv.T hlwb zoo li cov tub rog, rhuav tshem covinvaders uas lub system txawj ntse tau txheeb xyuas.
Chimeric antigen receptor (CAR) T cell technology: yog ib hom kev saws tes ntawm tesimmunotherapy (ACI).Tus neeg mob T cell nthuav qhia CAR los ntawm kev tsim kho caj cesthev naus laus zis, uas ua rau cov nyhuv T-hlwb raug tsom ntau dua, ua rau tuag taus thiab tsis tu ncuaCov kab mob sib kis tau zoo, thiab tuaj yeem kov yeej hauv zos immunosuppressive microenvironment ntawmqog nqaij hlav thiab rhuav tshem lub cev tiv thaiv kab mob.Qhov no yog ib qho kev tiv thaiv kab mob tiv thaiv kab mob qog noj ntshav.
Lub hauv paus ntsiab lus ntawm CART yog tshem tawm "ib txwm version" ntawm tus neeg mob lub cev tiv thaiv kab mob Tthiab ua haujlwm gene engineering, sib sau ua ke hauv vitro rau cov qog tshwj xeeb ntawm lub hom phiaj lojantipersonnel riam phom "chimeric antigen receptor (CAR)", thiab tom qab ntawd infuse cov hloov T hlwbrov qab mus rau hauv tus neeg mob lub cev, hloov kho cell receptors tshiab yuav zoo li rau nruab ib lub radar system,uas muaj peev xwm coj T hlwb nrhiav thiab rhuav tshem cov qog nqaij hlav cancer.
Qhov zoo ntawm CART ntawm BPIH
Vim qhov sib txawv ntawm cov qauv ntawm cov teeb liab intracellular, CAR tau tsim plaubtiam.Peb siv CART tiam tshiab.
1sttiam: Tsuas muaj ib qho teeb liab intracellular tivthaiv thiab cov qog inhibitioncuam tshuam tsis zoo.
2ndtiam: Ntxiv ib co-stimulating molecule nyob rau hauv lub hauv paus ntawm thawj tiam, thiab covLub peev xwm ntawm T hlwb los tua cov qog tau txhim kho.
3rdtiam: Raws li qhov thib ob tiam ntawm CAR, lub peev xwm ntawm T hlwb los inhibit qogKev loj hlob thiab txhawb kev apoptosis tau txhim kho zoo.
4thtiam: CAR-T hlwb tuaj yeem koom nrog hauv kev tshem tawm cov qog cell los ntawmactivating downstream transcription factor NFAT induce interleukin-12 tom qab CARpaub lub hom phiaj antigen.
| Tiam | Kev txhawb siab Qhov xwm txheej | Feature |
| 1st | cd 3 ua | Kev ua kom T cell tshwj xeeb, cytotoxic T cell, tab sis tsis tuaj yeem loj hlob thiab muaj sia nyob hauv lub cev. |
| 2nd | CD3ζ+CD28/4-1BB/OX40 | Ntxiv costimulator, txhim kho cell toxicity, txwv tsis pub muaj peev xwm. |
| 3rd | CD3ζ+CD28/4-1BB/OX40+CD134/CD137 | Ntxiv 2 costimulators, txhim khoproliferation muaj peev xwm thiab toxicity. |
| 4th | Suicide gene/Amored CAR-T (12IL) Mus CAR-T | Ua ke cov noob tua tus kheej, qhia txog kev tiv thaiv kab mob thiab lwm yam kev tswj xyuas meej. |
Txoj kev kho mob
1) Cov qe ntshav dawb cais tawm: Tus neeg mob T hlwb raug cais tawm ntawm cov ntshav peripheral.
2) T cells activation: magnetic hlaws (cov pob txha dendritic) coated nrog cov tshuaj tiv thaiv yogsiv los qhib T hlwb.
3) Transfection: T hlwb yog tsim los ntawm genetic engineering los qhia CAR hauv vitro.
4) Amplification: Cov noob caj noob ces hloov T cells yog amplified hauv vitro.
5) Chemotherapy: Tus neeg mob tau kho ua ntej nrog kev kho mob ua ntej T cell reinfusion.
6) Re-infusion: Genetically hloov T cells infuse rov qab rau hauv tus neeg mob.
Cov lus qhia
Indications rau CAR-T
Cov kab mob ua pa: mob ntsws cancer (mob cell carcinoma, squamous cell carcinoma,adenocarcinoma), mob qog noj ntshav nasopharynx, thiab lwm yam.
Digestive system: daim siab, plab thiab mob qog noj ntshav, thiab lwm yam.
Urinary system: raum thiab adrenal carcinoma thiab metastatic cnacer, thiab lwm yam.
Cov kab mob hauv cov ntshav: mob qog nqaij hlav thiab mob ntev (T lymphomaexcluded) thiab lwm yam.
Lwm yam mob qog noj ntshav: Malignant melanoma, mis, prostae thiab tus nplaig mob cancer, thiab lwm yam.
Kev phais kom tshem tawm cov kab mob thawj zaug, tab sis kev tiv thaiv tsis tshua muaj, thiab rov ua dua tshiab yog qeeb.
Cov qog nqaij hlav uas nthuav dav metastasis uas tsis tuaj yeem ua kev phais.
Cov kev mob tshwm sim ntawm chemotherapy thiab radiotherapy yog qhov loj lossis tsis hnov tsw rau chemotherapy thiab radiotherapy.
Tiv thaiv kom tsis txhob mob qog nqaij hlav tom qab phais, kws khomob thiab kws khomob.
Qhov zoo
1) CAR T hlwb yog lub hom phiaj heev thiab tuaj yeem tua cov qog hlwb nrog antigen tshwj xeeb zoo dua.
2) CAR-T cell kho yuav tsum tau siv sij hawm tsawg.CAR T xav kom lub sij hawm luv tshaj plaws rau kab lis kev cai T hlwb vim tias nws yuav tsum muaj cov hlwb tsawg dua nyob rau hauv tib txoj kev kho mob.Lub voj voog vitro kab lis kev cai tuaj yeem ua luv luv rau 2 lub lis piam, uas txo lub sijhawm tos.
3) CAR tuaj yeem lees paub tsis yog peptide antigens nkaus xwb, tab sis kuj muaj suab thaj thiab lipid antigens, nthuav dav lub hom phiaj ntawm cov qog antigens.CAR T therapy kuj tsis txwv los ntawm cov protein antigens ntawm cov qog hlwb.CAR T tuaj yeem siv cov piam thaj thiab lipid uas tsis yog-protein antigens ntawm cov qog hlwb los txheeb xyuas cov antigens hauv ntau qhov ntev.
4) CAR-T muaj qee qhov dav - spectrum reproducibility.Txij li qee qhov chaw tau nthuav tawm hauv ntau lub qog qog, xws li EGFR, CAR gene rau cov tshuaj tiv thaiv no tuaj yeem siv dav thaum nws tsim.
5) CAR T hlwb muaj lub cev tiv thaiv kab mob ua haujlwm thiab tuaj yeem muaj sia nyob hauv lub cev tau ntev.Nws yog ib qho tseem ceeb heev rau kev kho mob los tiv thaiv qog nqaij hlav.