CAR-T (Chimeric Antigen Receptor T-cell) ke eng?
Sa pele, a re hlahlobeng tsamaiso ea 'mele ea ho itšireletsa mafung ea motho.
Sistimi 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, tse boetseng li bitsoa li-leukocyte, tse tlang ka mefuta e 'meli ea motheo e kopanang ho batla le ho timetsa lintho tse bakang mafu.
Mefuta e 'meli ea mantlha ea li-leukocyte ke:
Ø li-phagocyte, lisele tse hlafunang lintho tse hlaselang
Ø Li-lymphocyte, lisele tse lumellang 'mele ho hopola le ho lemoha bahlaseli ba pele le ho thusa' mele ho li timetsa
Lisele tse 'maloa tse fapaneng li nkoa e le li-phagocyte. Mofuta o tloaelehileng haholo ke neutrophil, e loantšang libaktheria haholo-holo. 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-neutrophil tse bakoang ke tšoaetso. Mefuta e meng ea li-phagocyte e na le mesebetsi ea eona ea ho netefatsa hore 'mele o arabela ka nepo ho mofuta o itseng oa mohlaseli.
Mefuta e 'meli ea li-lymphocyte ke li-lymphocyte tsa B le li-lymphocyte tsa T. Li-lymphocyte li qala mokong oa masapo 'me li lula moo ebe lia hola ho ba lisele tsa B, kapa lia tloha ho ea tšoeleseng ea thymus, moo li holang ho ba lisele tsa T. Li-lymphocyte tsa B le li-lymphocyte tsa T li na le mesebetsi e fapaneng: Li-lymphocyte tsa B li tšoana le sistimi ea bohlale ea sesole ea 'mele, li batla lipheo tsa tsona 'me li romela tšireletso ho li notlela. Lisele tsa T li tšoana le masole, li timetsa bahlaseli bao sistimi ea bohlale e ba hlwaileng.
Sistimi 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, tse boetseng li bitsoa li-leukocyte, tse tlang ka mefuta e 'meli ea motheo e kopanang ho batla le ho timetsa lintho tse bakang mafu.
Mefuta e 'meli ea mantlha ea li-leukocyte ke:
Ø li-phagocyte, lisele tse hlafunang lintho tse hlaselang
Ø Li-lymphocyte, lisele tse lumellang 'mele ho hopola le ho lemoha bahlaseli ba pele le ho thusa' mele ho li timetsa
Lisele tse 'maloa tse fapaneng li nkoa e le li-phagocyte. Mofuta o tloaelehileng haholo ke neutrophil, e loantšang libaktheria haholo-holo. 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-neutrophil tse bakoang ke tšoaetso. Mefuta e meng ea li-phagocyte e na le mesebetsi ea eona ea ho netefatsa hore 'mele o arabela ka nepo ho mofuta o itseng oa mohlaseli.
Mefuta e 'meli ea li-lymphocyte ke li-lymphocyte tsa B le li-lymphocyte tsa T. Li-lymphocyte li qala mokong oa masapo 'me li lula moo ebe lia hola ho ba lisele tsa B, kapa lia tloha ho ea tšoeleseng ea thymus, moo li holang ho ba lisele tsa T. Li-lymphocyte tsa B le li-lymphocyte tsa T li na le mesebetsi e fapaneng: Li-lymphocyte tsa B li tšoana le sistimi ea bohlale ea sesole ea 'mele, li batla lipheo tsa tsona 'me li romela tšireletso ho li notlela. Lisele tsa T li tšoana le masole, li timetsa bahlaseli bao sistimi ea bohlale e ba hlwaileng.
Theknoloji ea lisele tsa T tsa Chimeric antigen receptor (CAR): ke mofuta oa kalafo ea immunotherapy ea sele e amoheloang (ACI). Lisele tsa T tsa mokuli li hlahisa CAR ka theknoloji ea ho aha liphatsa tsa lefutso, e leng se etsang hore lisele tsa T tse sebetsang li shebane haholoanyane, li be kotsi ebile li tšoarelle ho feta lisele tse tloaelehileng tsa 'mele,' me li ka hlōla tikoloho e nyenyane ea ho thibela 'mele ea hlahala le ho senya mamello ea 'mele ea moamoheli. Ena ke phekolo e khethehileng ea ho thibela hlahala ea lisele tsa 'mele.
Molao-motheo oa CART ke ho ntša "mofuta o tloaelehileng" oa lisele tsa T tsa 'mele tsa mokuli le ho tsoela pele ka boenjiniere ba liphatsa tsa lefutso, ho bokella ka vitro bakeng sa lipheo tse ikhethileng tsa hlahala tsa libetsa tse kholo tsa antipersonnel "chimeric antigen receptor (CAR)", ebe o kenya lisele tsa T tse fetotsoeng 'meleng oa mokuli, li-receptor tse ncha tse fetotsoeng tsa sele 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 dipharologanyo tse teng sebopehong sa letshwao la ka hare ho sele, CAR e ntshetse pele meloko e mene. Re sebedisa CART ya moloko wa moraorao.
1stmoloko: Ho ne ho e-na le karolo e le 'ngoe feela ea lets'oao la ka hare ho sele 'me phello ea thibelo ea hlahala e ne e le mpe.
2ndmoloko: Ho ekelitsoe molek'hule e susumetsang hammoho motheong oa moloko oa pele, 'me bokhoni ba lisele tsa T ba ho bolaea lihlahala bo ntlafalitsoe.
3rdmoloko: Ho latela moloko oa bobeli oa CAR, bokhoni ba lisele tsa T ba ho thibela ho ata ha hlahala le ho khothaletsa apoptosis bo ntlafalitsoe haholo.
4thMoloko: Lisele tsa CAR-T li ka ameha ho tloseng palo ea lisele tsa hlahala ka ho kenya tšebetsong NFAT ea transcription factor e ka tlase ho motsamao ho hlahisa interleukin-12 kamora hore CAR e lemohe antigen e reriloeng.
Mokhoa oa phekolo
1) Ho aroloa ha lisele tse tšoeu tsa mali: Lisele tsa T tsa mokuli li aroloa maling a ka ntle;
2) Ho kenngwa tshebetsong ha disele tsa T: dibead tsa makenete (disele tsa dendritic tsa maiketsetso) tse manehilweng ka di-antibodies di sebediswa ho kenya tshebetsong disele tsa T;
Phetoho: Lisele tsa T li entsoe ka liphatsa tsa lefutso ho hlahisa CAR ka ntle ho 'mele.
3) Ho atolosoa ha lisele: Lisele tsa T tse fetotsoeng liphatsa tsa lefutso lia atolosoa ka hare ho 'mele.
4) Kalafo ea Chemotherapy: Mokuli o phekoloa esale pele ka chemotherapy pele ho kenngoa lisele tsa T hape;
5) Ho kenngoa hape: Lisele tsa T tse fetotsoeng liphatsa tsa lefutso li khutlela ho mokuli.
Melemo:
1)Lisele tsa CAR T li reretsoe haholo 'me li ka bolaea lisele tsa hlahala tse nang le antigen e khethehileng ka katleho e kholo.
2)Kalafo ea lisele tsa CAR-T e hloka nako e nyane. CAR T e hloka nako e khutšoanyane ka ho fetisisa ea ho lema lisele tsa T hobane e hloka lisele tse fokolang tlas'a phello e tšoanang ea kalafo. Potoloho ea ho lema ka vitro e ka khutsufatsoa ho libeke tse 2, e leng se ileng sa fokotsa nako ea ho leta haholo.
3)CAR e ka lemoha eseng feela li-antigen tsa peptide, empa hape le li-antigen tsa tsoekere le lipid, e atolosa mefuta e reriloeng ea li-antigen tsa hlahala. Kalafo ea CAR T ha e lekanyetsoe ke li-antigen tsa protheine tsa lisele tsa hlahala. CAR T e ka sebelisa li-antigen tsa tsoekere le lipid tse seng tsa protheine tsa lisele tsa hlahala ho khetholla li-antigen ka litekanyo tse fapaneng.
4)CAR-T e na le bokgoni bo itseng ba ho ikatisa ka bongata. Kaha libaka tse itseng di hlahiswa diseleng tse ngata tsa hlahala, tse kang EGFR, jini ya CAR bakeng sa antigen ena e ka sebediswa haholo hang ha e se e hahilwe.
5)Lisele tsa CAR T li na le ts'ebetso ea ho hopola 'mele' me li ka phela 'meleng nako e telele. Ho bohlokoa haholo ho thibela ho khutla ha hlahala.