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 kab mob uas ua haujlwm ua ke lostiv thaiv lub cev. Ib qho ntawm cov hlwb tseem ceeb uas koom nrog yog cov hlwb 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 ua rau muaj kab mob lossiscov tshuaj.
Ob hom leukocytes tseem ceeb yog:
Cov phagocytes, cov hlwb uas zom cov kab mob uas nkag mus rau hauv lub cev.
Lymphocytes, cov hlwb uas tso cai rau lub cev nco qab thiab paub txog cov neeg tawm tsam yav dhau los thiab pablub cev ua rau lawv puas tsuaj.
Muaj ntau hom hlwb sib txawv uas suav tias yog phagocytes. Hom uas pom ntau tshaj plaws yog neutrophil,uas feem ntau tawm tsam cov kab mob bacteria. Yog tias cov kws kho mob txhawj xeeb txog kev kis kab mob bacterial, lawv yuav xaj kom muaj kev kho mobkuaj ntshav seb 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 neeg ntxeem tau tshwj xeeb.
Ob hom lymphocytes yog B lymphocytes thiab T lymphocytes. Lymphocytes pib tawmnyob rau hauv cov pob txha pob txha thiab nyob ntawd thiab loj hlob mus rau hauv B hlwb, lossis lawv tawm mus rau thymusqog, qhov chaw uas lawv loj hlob mus ua T cell. B lymphocytes thiab T lymphocytes muaj kev sib caiskev ua haujlwm: B lymphocytes zoo li lub cev lub cev txawj ntse tub rog, nrhiav lawv covcov hom phiaj thiab xa cov kev tiv thaiv los xauv rau lawv. Cov qe ntshav T zoo li cov tub rog, rhuav tshem covcov neeg nkag tebchaws uas lub tshuab txawj ntse tau txheeb xyuas.
Kev siv tshuab Chimeric antigen receptor (CAR) T cell: yog ib hom cellular uas siv los ua qauvkev kho mob tiv thaiv kab mob (ACI). Tus neeg mob lub T cell express CAR los ntawm kev tsim kho caj cesthev naus laus zis, uas ua rau cov qe ntshav T effector muaj lub hom phiaj ntau dua, ua rau tuag taus thiab ruaj khov dua licov hlwb tiv thaiv kab mob ib txwm muaj, thiab tuaj yeem kov yeej cov chaw ib puag ncig tiv thaiv kab mob hauv zos ntawmqog nqaij hlav thiab kev tiv thaiv kab mob ntawm tus kab mob. Qhov no yog kev kho mob tshwj xeeb rau cov qe ntshav dawb tiv thaiv kab mob.
Lub hauv paus ntsiab lus ntawm CART yog rho tawm "tus qauv ib txwm" ntawm tus neeg mob tus kheej lub cev tiv thaiv kab mob T hlwbthiab txuas ntxiv kev tsim kho noob caj noob ces, sib sau ua ke hauv vitro rau cov hom phiaj tshwj xeeb ntawm cov qog lojriam phom tua neeg "chimeric antigen receptor (CAR)", thiab tom qab ntawd muab cov T cell uas hloov pauv lawm tso rau hauvrov qab mus rau hauv tus neeg mob lub cev, cov cell receptors tshiab uas tau hloov kho yuav zoo li teeb tsa lub radar system,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 yog qhov sib txawv ntawm cov qauv ntawm cov cim qhia hauv lub hlwb, CAR tau tsim plaubtiam neeg. Peb siv CART tiam tshiab kawg.
1sttiam neeg: Tsuas muaj ib qho khoom siv teeb liab hauv lub hlwb thiab kev tiv thaiv qog nqaij hlavcov nyhuv tsis zoo.
2ndtiam neeg: Ntxiv ib lub molecule co-stimulating raws li thawj tiam neeg, thiablub peev xwm ntawm cov qe ntshav T 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 qog noj ntshavkev loj hlob thiab txhawb nqa apoptosis tau zoo dua qub.
4thtiam neeg: CAR-T cell tuaj yeem koom nrog kev tshem tawm cov qog nqaij hlav los ntawmqhib lub downstream transcription factor NFAT kom induce interleukin-12 tom qab CARlees paub lub hom phiaj antigen.
| Tiam neeg | Kev txhawb zog Qhov tseem ceeb | Feature |
| 1st | CD3Z | Kev ua haujlwm tshwj xeeb ntawm T cell, 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 cov cell toxicity, txwv proliferation peev xwm. |
| 3rd | CD3ζ+CD28/4-1BB/OX40+CD134 /CD137 | Ntxiv 2 lub costimulators, txhim khomuaj peev xwm nthuav dav thiab lom. |
| 4th | Kev tua tus kheej gene/Amored CAR-T (12IL) Mus CAR-T | Ua ke cov noob caj noob ces tua tus kheej, qhia txog kev tiv thaiv kab mob thiab lwm yam kev ntsuas tswj hwm meej. |
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 yogsiv los ua kom cov T cell ua haujlwm.
3) Kev Hloov Pauv: Cov qe ntshav T raug tsim kho kom pom tseeb CAR hauv vitro.
4) Kev Ua Kom Loj Hlob: Cov qe ntshav T uas tau hloov kho caj ces raug ua kom loj hlob hauv vitro.
5) Kev Kho Mob Chemotherapy: Tus neeg mob raug kho nrog chemotherapy ua ntej ua ntej rov txhaj tshuaj T cell.
6) Rov txhaj tshuaj dua: Cov qe ntshav T uas tau hloov kho caj ces rov txhaj tshuaj dua rau hauv tus neeg mob.
Cov cim qhia
Cov cim qhia rau CAR-T
Kev ua pa: Mob qog nqaij hlav ntsws (mob qog nqaij hlav me, mob qog nqaij hlav squamous,adenocarcinoma), mob qog nqaij hlav ntawm lub qhov ntswg, thiab lwm yam.
Kev zom zaub mov: Mob qog noj ntshav hauv siab, plab thiab colorectal, thiab lwm yam.
Cov kab mob tso zis: Mob qog nqaij hlav thiab mob qog adrenal thiab mob qog nqaij hlav metastatic, thiab lwm yam.
Cov kab mob ntshav: Mob ntshav dawb lymphoblastic mob hnyav thiab mob ntev (T lymphoma)tsis suav nrog) thiab lwm yam.
Lwm yam mob qog noj ntshav: Mob qog nqaij hlav melanoma, mob qog nqaij hlav mis, mob qog nqaij hlav prostae thiab mob qog nqaij hlav tus nplaig, thiab lwm yam.
Phais mob kom tshem tawm qhov mob tseem ceeb, tab sis lub zog tiv thaiv kab mob qis, thiab kev rov zoo qeeb.
Cov qog nqaij hlav uas muaj metastasis dav dav uas tsis tuaj yeem ua phais.
Cov kev phiv los ntawm kev siv tshuaj chemotherapy thiab radiotherapy yog loj lossis tsis muaj kev cuam tshuam rau kev siv tshuaj chemotherapy thiab radiotherapy.
Tiv thaiv kom tsis txhob rov qab mob qog tom qab phais, chemotherapy thiab radiotherapy.
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 rau qhov tshwj xeeb ntawm cov antigen 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 rau 2 lub lis piam, uas ua rau lub sijhawm tos luv dua.
3) CAR tsis yog tsuas paub txog cov peptide antigens xwb, tab sis kuj paub txog cov suab thaj thiab lipid antigens, nthuav dav ntau yam ntawm cov antigens qog. Kev kho mob CAR T kuj tsis txwv los ntawm cov protein antigens ntawm cov hlwb qog. CAR T tuaj yeem siv cov suab thaj thiab lipid uas tsis yog protein antigens ntawm cov hlwb qog 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 kev rov qab mob qog noj ntshav.