CAR-T (Chimeric Antigen Receptor T-cell) ke eng?
Sa ntlha, a re sekasekeng thulaganyo ya motho ya go lwantsha malwetse.
Tsamaiso ea 'mele ea ho itšireletsa mafung e entsoe ka marang-rang a lisele, lisele le litho tse sebetsang hammoho ho sireletsa' mele.E 'ngoe ea lisele tsa bohlokoa tse amehang ke lisele tse tšoeu tsa mali, tseo hape li bitsoang leukocyte, tse tlang ka mefuta e 'meli ea motheo e kopanang ho batla le ho senya likokoana-hloko kapa lintho tse bakang maloetse.
Mefuta e 'meli ea mantlha ea leukocyte ke:
Ø phagocyte, lisele tse hlafunang likokoana-hloko tse hlaselang
Ø li-lymphocyte, lisele tse lumellang 'mele ho hopola le ho lemoha bahlaseli ba pele le ho thusa' mele ho ba senya
Lisele tse ngata tse fapaneng li nkoa e le li-phagocyte.Mofuta o tloaelehileng haholo ke neutrophil, eo haholo-holo e loantšang libaktheria.Haeba lingaka li tšoenyehile ka tšoaetso ea baktheria, li ka 'na tsa laela tlhahlobo ea mali ho bona hore na mokuli o na le palo e eketsehileng ea li-neutrophils tse bakoang ke tšoaetso.Mefuta e meng ea phagocyte e na le mesebetsi ea eona ea ho etsa bonnete ba hore 'mele o arabela ka mokhoa o nepahetseng ho mofuta o itseng oa bahlaseli.
Mefuta e 'meli ea li-lymphocyte ke B lymphocyte le T lymphocyte.Li-lymphocyte li qala mokong oa masapo ebe li lula moo ebe li hōla ho ba lisele tsa B, kapa li tloha ho ea thymus gland, moo li hōlang ho ba T liseleng.Li-lymphocyte tsa B le T lymphocyte li na le mesebetsi e fapaneng: Li-lymphocyte tsa B li tšoana le tsamaiso ea 'mele ea sesole sa sesole, e batlang sepheo sa eona le ho romela litšireletso ho li notlela.Lisele tsa T li tšoana le masole, li senya bahlaseli bao tsamaiso ea bohlale e ba khethileng.
Tsamaiso ea 'mele ea ho itšireletsa mafung e entsoe ka marang-rang a lisele, lisele le litho tse sebetsang hammoho ho sireletsa' mele.E 'ngoe ea lisele tsa bohlokoa tse amehang ke lisele tse tšoeu tsa mali, tseo hape li bitsoang leukocyte, tse tlang ka mefuta e 'meli ea motheo e kopanang ho batla le ho senya likokoana-hloko kapa lintho tse bakang maloetse.
Mefuta e 'meli ea mantlha ea leukocyte ke:
Ø phagocyte, lisele tse hlafunang likokoana-hloko tse hlaselang
Ø li-lymphocyte, lisele tse lumellang 'mele ho hopola le ho lemoha bahlaseli ba pele le ho thusa' mele ho ba senya
Lisele tse ngata tse fapaneng li nkoa e le li-phagocyte.Mofuta o tloaelehileng haholo ke neutrophil, eo haholo-holo e loantšang libaktheria.Haeba lingaka li tšoenyehile ka tšoaetso ea baktheria, li ka 'na tsa laela tlhahlobo ea mali ho bona hore na mokuli o na le palo e eketsehileng ea li-neutrophils tse bakoang ke tšoaetso.Mefuta e meng ea phagocyte e na le mesebetsi ea eona ea ho etsa bonnete ba hore 'mele o arabela ka mokhoa o nepahetseng ho mofuta o itseng oa bahlaseli.
Mefuta e 'meli ea li-lymphocyte ke B lymphocyte le T lymphocyte.Li-lymphocyte li qala mokong oa masapo ebe li lula moo ebe li hōla ho ba lisele tsa B, kapa li tloha ho ea thymus gland, moo li hōlang ho ba T liseleng.Li-lymphocyte tsa B le T lymphocyte li na le mesebetsi e fapaneng: Li-lymphocyte tsa B li tšoana le tsamaiso ea 'mele ea sesole sa sesole, e batlang sepheo sa eona le ho romela litšireletso ho li notlela.Lisele tsa T li tšoana le masole, li senya bahlaseli bao tsamaiso ea bohlale e ba khethileng.
Chimeric antigen receptor(CAR) T cell technology: ke mofuta oa adoptive cellular immunotherapy(ACI).T cell ea mokuli e hlahisa CAR ka thekenoloji ea ho tsosolosa liphatsa tsa lefutso, e etsang hore lisele tsa T tsa phello li lebisitsoe haholoanyane, li bolaee ebile li phehelle ho feta lisele tse tloaelehileng tsa ho itšireletsa mafung, 'me li ka hlōla likokoana-hloko tsa sebakeng seo immunosuppressive microenvironment ea hlahala le ho senya mamello ea ho itšireletsa mafung.Ena ke kalafo e khethehileng ea 'mele ea ho itšireletsa mafung.
Molao-motheo oa CART ke ho ntša "mofuta o tloaelehileng" oa lisele tsa T tsa mokuli tsa 'mele le ho tsoela pele ka boenjiniere ba liphatsa tsa lefutso, ho bokella in vitro bakeng sa liphofu tse khethehileng tsa sebetsa se seholo sa antipersonnel "chimeric antigen receptor (CAR)", ebe se kenya phetoho e fetotsoeng. Lisele tsa T li khutlela 'meleng oa mokuli, li-receptor tse ncha tse fetotsoeng li tla tšoana le ho kenya sistimi ea radar, e khonang ho tataisa lisele tsa T ho fumana le ho senya lisele tsa mofetše.
Molemo oa CART ho BPIH
Ka lebaka la liphapang tsa sebopeho sa sebaka sa matšoao a intracellular, CAR e thehile meloko e mene.Re sebelisa CART ea morao-rao ea moloko.
1Stmoloko: Ho ne ho e-na le karolo e le 'ngoe feela ea matšoao a intracellular mme phello ea ho thibela tumor e ne e fokola.
2ndmoloko: Ho ekelitsoe molek'hule e kopanyang motheong oa moloko oa pele, 'me bokhoni ba lisele tsa T ho bolaea lihlahala bo ile ba ntlafatsoa.
3rdmoloko: Ho itšetlehile ka moloko oa bobeli oa CAR, bokhoni ba lisele tsa T ho thibela ho ata ha hlahala le ho khothalletsa apoptosis bo ile ba ntlafala haholo.
4thmoloko: Lisele tsa CAR-T li ka kenya letsoho ho hlakoloeng ha palo ea lisele tsa tumor ka ho kenya karolo e tlase ea transcription factor NFAT ho kenya interleukin-12 ka mor'a hore CAR e lemohe antigen e lebisitsoeng.
Mokhoa oa phekolo
1) Ho itšehla thajana ha lisele tse tšoeu tsa mali: Lisele tsa T tsa mokuli li arohane le mali a peripheral;
2) Ts'ebetso ea lisele tsa T: lifaha tsa makenete (lisele tsa maiketsetso tsa dendritic) tse koahetsoeng ka li-antibodies li sebelisetsoa ho kenya lisele tsa T;
Phetoho: Lisele tsa T li entsoe ka liphatsa tsa lefutso ho hlahisa CAR in vitro.
3) Amplification: Lisele tsa T tse fetotsoeng ka liphatsa tsa lefutso li holisoa ka in vitro.
4) Chemotherapy: Mokuli o phekoloa ka chemotherapy pele ho T cell reinfusion;
5) Ho tšeloa hape: Lisele tsa T tse fetotsoeng ka liphatsa tsa lefutso li khutlisetsa ho mokuli.
Melemo:
1)Lisele tsa CAR T li lebisitsoe haholo 'me li ka bolaea lisele tsa hlahala ka mokhoa o ikhethileng oa antigen ka katleho.
2)Kalafo ea lisele tsa CAR-T e hloka nako e nyane.CAR T e hloka nako e khuts'oane ho feta liseleng tsa T tsa setso hobane e hloka lisele tse fokolang tlas'a phello e tšoanang ea phekolo.The vitro culture cycle e ka khutsufatsoa ho libeke tse 2, e leng se ileng sa fokotsa haholo nako ea ho leta.
3)CAR ha e khone ho lemoha li-antigen tsa peptide feela, empa hape le tsoekere le li-antigen tsa lipid, ho holisa sepheo sa li-antigen tsa tumor.Phekolo ea CAR T le eona ha e felle feela ke li-antigen tsa protheine tsa lisele tsa tumor.CAR T e ka sebelisa li-antigens tsa tsoekere le lipid tse se nang protheine tsa lisele tsa tumor ho tsebahatsa li-antigen ka litekanyo tse ngata.
4)CAR-T e na le bophara bo itseng - spectrum reproducibility.Kaha libaka tse ling li hlahisoa ka lisele tse ngata tsa hlahala, tse kang EGFR, gene ea CAR bakeng sa antigen ena e ka sebelisoa haholo ha e se e hahiloe.
5)Lisele tsa CAR T li na le ts'ebetso ea mohopolo oa 'mele oa ho itšireletsa mafung' me li ka phela 'meleng nako e telele.Ke ea bohlokoa haholo kliniking ho thibela ho hlaha ha hlahala.