CAR-T (Chimeric Antigen Receptor T-cell) yog dab tsi?
Ua ntej, cia peb los saib seb tib neeg lub cev tiv thaiv kab mob zoo li cas.
Lub cev tiv thaiv kab mob yog tsim los ntawm ib lub network ntawm cov hlwb, cov nqaij, thiab cov kabmob uas ua haujlwm ua ke los tiv thaiv lub cev. Ib qho ntawm cov hlwb tseem ceeb uas koom nrog yog cov qe ntshav dawb, tseem hu ua leukocytes, uas muaj ob hom yooj yim uas sib xyaw ua ke los nrhiav thiab rhuav tshem cov kab mob lossis cov tshuaj uas ua rau muaj kab mob.
Ob hom leukocytes tseem ceeb yog:
Ø phagocytes, cov hlwb uas zom cov kab mob uas nkag mus rau hauv lub cev
Ø lymphocytes, cov hlwb uas tso cai rau lub cev nco qab thiab paub txog cov neeg tawm tsam yav dhau los thiab pab lub cev rhuav tshem lawv
Muaj ntau hom hlwb sib txawv uas suav tias yog phagocytes. Hom uas feem ntau pom yog neutrophil, uas feem ntau tawm tsam cov kab mob. Yog tias cov kws kho mob txhawj xeeb txog kev kis kab mob, lawv yuav hais kom kuaj ntshav kom pom tias tus neeg mob puas muaj cov neutrophils ntau ntxiv los ntawm kev kis kab mob. Lwm hom phagocytes muaj lawv txoj haujlwm kom paub tseeb tias lub cev teb tau zoo rau ib hom kab mob tshwj xeeb.
Ob hom lymphocytes yog B lymphocytes thiab T lymphocytes. Lymphocytes pib tawm hauv cov pob txha pob txha thiab nyob ntawd thiab loj hlob mus rau hauv B cell, lossis lawv tawm mus rau thymus gland, qhov chaw uas lawv loj hlob mus rau hauv T cell. B lymphocytes thiab T lymphocytes muaj cov haujlwm sib cais: B lymphocytes zoo li lub cev tub rog lub cev txawj ntse, nrhiav lawv cov hom phiaj thiab xa cov kev tiv thaiv mus xauv rau lawv. T cell zoo li cov tub rog, rhuav tshem cov neeg tawm tsam uas lub cev txawj ntse tau txheeb xyuas.
Lub cev tiv thaiv kab mob yog tsim los ntawm ib lub network ntawm cov hlwb, cov nqaij, thiab cov kabmob uas ua haujlwm ua ke los tiv thaiv lub cev. Ib qho ntawm cov hlwb tseem ceeb uas koom nrog yog cov qe ntshav dawb, tseem hu ua leukocytes, uas muaj ob hom yooj yim uas sib xyaw ua ke los nrhiav thiab rhuav tshem cov kab mob lossis cov tshuaj uas ua rau muaj kab mob.
Ob hom leukocytes tseem ceeb yog:
Ø phagocytes, cov hlwb uas zom cov kab mob uas nkag mus rau hauv lub cev
Ø lymphocytes, cov hlwb uas tso cai rau lub cev nco qab thiab paub txog cov neeg tawm tsam yav dhau los thiab pab lub cev rhuav tshem lawv
Muaj ntau hom hlwb sib txawv uas suav tias yog phagocytes. Hom uas feem ntau pom yog neutrophil, uas feem ntau tawm tsam cov kab mob. Yog tias cov kws kho mob txhawj xeeb txog kev kis kab mob, lawv yuav hais kom kuaj ntshav kom pom tias tus neeg mob puas muaj cov neutrophils ntau ntxiv los ntawm kev kis kab mob. Lwm hom phagocytes muaj lawv txoj haujlwm kom paub tseeb tias lub cev teb tau zoo rau ib hom kab mob tshwj xeeb.
Ob hom lymphocytes yog B lymphocytes thiab T lymphocytes. Lymphocytes pib tawm hauv cov pob txha pob txha thiab nyob ntawd thiab loj hlob mus rau hauv B cell, lossis lawv tawm mus rau thymus gland, qhov chaw uas lawv loj hlob mus rau hauv T cell. B lymphocytes thiab T lymphocytes muaj cov haujlwm sib cais: B lymphocytes zoo li lub cev tub rog lub cev txawj ntse, nrhiav lawv cov hom phiaj thiab xa cov kev tiv thaiv mus xauv rau lawv. T cell zoo li cov tub rog, rhuav tshem cov neeg tawm tsam uas lub cev txawj ntse tau txheeb xyuas.
Kev siv tshuab Chimeric antigen receptor (CAR) T cell technology: yog ib hom kev kho mob cellular immunotherapy (ACI). Tus neeg mob T cell qhia CAR los ntawm kev siv tshuab genetic reconstruction, uas ua rau cov effector T cell muaj lub hom phiaj ntau dua, ua rau tuag taus thiab ruaj khov dua li cov cell tiv thaiv kab mob ib txwm muaj, thiab tuaj yeem kov yeej qhov chaw ib puag ncig ntawm cov qog nqaij hlav thiab rhuav tshem kev tiv thaiv kab mob ntawm tus tswv tsev. Qhov no yog kev kho mob tshwj xeeb rau cov cell tiv thaiv kab mob tiv thaiv kab mob.
Lub hauv paus ntsiab lus ntawm CART yog rho tawm "cov qauv ib txwm" ntawm tus neeg mob tus kheej lub cev tiv thaiv kab mob T thiab txuas ntxiv kev tsim cov noob caj noob ces, sib sau ua ke hauv vitro rau cov hom phiaj tshwj xeeb ntawm cov qog nqaij hlav ntawm cov riam phom loj tiv thaiv neeg "chimeric antigen receptor (CAR)", thiab tom qab ntawd muab cov T cell hloov pauv rov qab rau hauv tus neeg mob lub cev, cov cell receptors hloov kho tshiab yuav zoo li teeb tsa lub kaw lus radar, uas muaj peev xwm coj cov T cell nrhiav thiab rhuav tshem cov cell mob qog noj ntshav.
Qhov zoo ntawm CART ntawm BPIH
Vim muaj qhov sib txawv ntawm cov qauv ntawm cov cim qhia hauv lub hlwb, CAR tau tsim plaub tiam neeg. Peb siv CART tiam tshiab kawg.
1sttiam neeg: Tsuas muaj ib qho khoom siv teeb liab hauv lub hlwb xwb thiab cov nyhuv tiv thaiv qog tsis zoo.
2ndtiam neeg: Ntxiv ib lub molecule co-stimulating raws li thawj tiam neeg, thiab lub peev xwm ntawm T cell los tua cov qog nqaij hlav tau zoo dua.
3rdtiam neeg: Raws li tiam neeg thib ob ntawm CAR, lub peev xwm ntawm T cell los tiv thaiv kev loj hlob ntawm qog thiab txhawb kev tuag ntawm cov hlwb tau zoo dua qub.
4thtiam neeg: CAR-T cov hlwb tuaj yeem koom nrog kev tshem tawm cov hlwb qog nqaij hlav los ntawm kev ua kom lub zog transcription factor NFAT ua haujlwm kom induce interleukin-12 tom qab CAR lees paub lub hom phiaj antigen.
Cov txheej txheem kho mob
1) Kev rho tawm cov qe ntshav dawb: Cov qe ntshav T ntawm tus neeg mob raug rho tawm ntawm cov ntshav ntawm sab nraud;
2) Kev ua kom cov qe ntshav T ua haujlwm: cov hlaws sib nqus (cov qe ntshav dendritic cuav) uas muaj cov tshuaj tiv thaiv kab mob siv los ua kom cov qe ntshav T ua haujlwm;
Kev Hloov Pauv: Cov qe ntshav T raug tsim kho kom muaj noob caj noob ces los qhia CAR hauv vitro.
3) Kev Ua Kom Loj Hlob: Cov qe ntshav T uas tau hloov kho caj ces raug ua kom loj hlob hauv vitro.
4) Kev Kho Mob Chemotherapy: Tus neeg mob raug kho nrog chemotherapy ua ntej ua ntej rov txhaj tshuaj T cell;
5) Rov txhaj tshuaj dua: Cov qe ntshav T uas tau hloov kho caj ces rov txhaj tshuaj dua rau hauv tus neeg mob.
Cov txiaj ntsig:
1)Cov qe ntshav CAR T yog cov qe ntshav uas raug tsom mus rau qhov tseem ceeb heev thiab tuaj yeem tua cov qe ntshav qog nrog cov antigen tshwj xeeb zoo dua.
2)Kev kho mob CAR-T cell siv sijhawm tsawg dua. CAR T siv sijhawm luv tshaj plaws los cog qoob loo T cell vim nws xav tau tsawg dua cell nyob rau hauv tib qho kev kho mob. Lub voj voog cog qoob loo hauv vitro tuaj yeem luv dua mus rau 2 lub lis piam, uas feem ntau txo lub sijhawm tos.
3)CAR tsis yog tsuas yog paub txog cov peptide antigens xwb, tab sis kuj paub txog cov suab thaj thiab lipid antigens, ua rau cov hom phiaj ntawm cov antigens qog nqaij hlav nthuav dav. Kev kho mob CAR T kuj tsis txwv los ntawm cov protein antigens ntawm cov hlwb qog nqaij hlav. CAR T tuaj yeem siv cov suab thaj thiab lipid uas tsis yog protein antigens ntawm cov hlwb qog nqaij hlav los txheeb xyuas cov antigens hauv ntau qhov ntev.
4)CAR-T muaj qee qhov kev ua rov ua dua dav dav. Vim tias qee qhov chaw tau qhia tawm hauv ntau lub hlwb qog, xws li EGFR, CAR gene rau cov antigen no tuaj yeem siv dav thaum nws tau tsim.
5)Cov qe ntshav CAR T muaj lub luag haujlwm nco qab ntawm lub cev thiab tuaj yeem nyob hauv lub cev tau ntev. Nws yog ib qho tseem ceeb heev rau kev kho mob kom tiv thaiv tau qhov mob qog rov qab los.