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 ke los tiv thaiv lub cev.Ib qho ntawm cov hlwb tseem ceeb koom nrog yog cov qe ntshav dawb, tseem hu ua leukocytes, uas tuaj hauv ob hom kev sib xyaw ua ke los nrhiav thiab rhuav tshem cov kab mob uas ua rau cov kab mob lossis cov khoom siv.
Qhov thib ob hom ntawm leukocytes yog:
Ø phagocytes, cov hlwb uas zom cov kab mob nkag mus
Ø lymphocytes, cov hlwb uas tso cai rau lub cev nco qab thiab paub txog cov neeg ua phem dhau los thiab pab lub 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 cov kws kho mob txhawj xeeb txog tus kab mob, lawv yuav xaj kom kuaj 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 los xyuas kom meej tias lub cev teb tau zoo rau ib hom invader.
Ob hom lymphocytes yog B lymphocytes thiab T lymphocytes.Lymphocytes pib tawm hauv cov pob txha thiab ob qho tib si nyob ntawd thiab loj hlob rau hauv B hlwb, los yog lawv tawm mus rau lub caj pas thymus, qhov chaw lawv loj hlob rau hauv T hlwb.B lymphocytes thiab T lymphocytes muaj cov haujlwm sib cais: B lymphocytes zoo li lub cev kev ua tub rog, nrhiav lawv lub hom phiaj thiab xa cov kev tiv thaiv los xauv rau lawv.T hlwb zoo li cov tub rog, rhuav tshem cov invaders uas cov kev txawj ntse tau txheeb xyuas.
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 ke los tiv thaiv lub cev.Ib qho ntawm cov hlwb tseem ceeb koom nrog yog cov qe ntshav dawb, tseem hu ua leukocytes, uas tuaj hauv ob hom kev sib xyaw ua ke los nrhiav thiab rhuav tshem cov kab mob uas ua rau cov kab mob lossis cov khoom siv.
Qhov thib ob hom ntawm leukocytes yog:
Ø phagocytes, cov hlwb uas zom cov kab mob nkag mus
Ø lymphocytes, cov hlwb uas tso cai rau lub cev nco qab thiab paub txog cov neeg ua phem dhau los thiab pab lub 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 cov kws kho mob txhawj xeeb txog tus kab mob, lawv yuav xaj kom kuaj 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 los xyuas kom meej tias lub cev teb tau zoo rau ib hom invader.
Ob hom lymphocytes yog B lymphocytes thiab T lymphocytes.Lymphocytes pib tawm hauv cov pob txha thiab ob qho tib si nyob ntawd thiab loj hlob rau hauv B hlwb, los yog lawv tawm mus rau lub caj pas thymus, qhov chaw lawv loj hlob rau hauv T hlwb.B lymphocytes thiab T lymphocytes muaj cov haujlwm sib cais: B lymphocytes zoo li lub cev kev ua tub rog, nrhiav lawv lub hom phiaj thiab xa cov kev tiv thaiv los xauv rau lawv.T hlwb zoo li cov tub rog, rhuav tshem cov invaders uas cov kev txawj ntse tau txheeb xyuas.
Chimeric antigen receptor (CAR) T cell thev naus laus zis: yog ib hom kev siv tshuaj tiv thaiv kab mob hlwb (ACI).Tus neeg mob T cell nthuav qhia CAR los ntawm kev tsim kho cov noob caj noob ces, uas ua rau cov nyhuv T cell muaj ntau lub hom phiaj, ua rau tuag taus thiab pheej ua rau lub cev tiv thaiv kab mob tsis zoo, thiab tuaj yeem kov yeej cov tshuaj tiv thaiv kab mob hauv zos microenvironment ntawm cov qog thiab ua rau 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 cov "ib txwm version" ntawm tus neeg mob tus kheej lub cev tiv thaiv kab mob T hlwb thiab ua haujlwm gene engineering, sib sau ua ke hauv vitro rau cov qog tshwj xeeb ntawm cov neeg tua neeg loj riam phom "chimeric antigen receptor (CAR)", thiab tom qab ntawd infuse qhov hloov pauv. T hlwb rov 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 cov 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 plaub tiam neeg.Peb siv CART tiam tshiab.
1sttiam: Tsuas muaj ib qho teeb liab intracellular tivthaiv thiab cov qog inhibition nyhuv tsis zoo.
2ndtiam: Ntxiv ib co-stimulating molecule nyob rau hauv lub hauv paus ntawm thawj tiam, thiab lub peev xwm ntawm T hlwb los tua cov qog tau txhim kho.
3rdtiam: Raws li lub thib ob tiam ntawm CAR, lub peev xwm ntawm T hlwb los inhibit qog proliferation thiab txhawb apoptosis tau loj hlob.
4thtiam: CAR-T hlwb tuaj yeem koom nrog hauv kev tshem tawm ntawm cov qog hlwb los ntawm kev ua kom cov kab mob qis qis NFAT ua rau muaj kev cuam tshuam interleukin-12 tom qab CAR pom lub hom phiaj antigen.
Txoj kev kho mob
1) Kev cais cov qe ntshav dawb: Tus neeg mob T hlwb raug cais tawm ntawm cov ntshav peripheral;
2) T hlwb ua kom: sib nqus hlaws (cov khoom siv dag zog) coated nrog cov tshuaj tiv thaiv yog siv los qhib T hlwb;
Kev hloov pauv: T hlwb yog tsim los tsim kho caj ces los qhia CAR hauv vitro.
3) Amplification: Cov noob caj noob ces hloov T cell yog amplified nyob rau hauv vitro.
4) Tshuaj Kho Mob: Tus neeg mob tau kho ua ntej nrog kev kho mob ua ntej T cell reinfusion;
5) Re-infusion: Genetically hloov T cells infuse rov qab rau hauv tus neeg mob.
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 therapy 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 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.