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 hosireletsa 'mele. E 'ngoe ea lisele tsa bohlokoa tse amehang ke lisele tse tšoeu tsa mali, tse bitsoang hape li-leukocyte,tse tlang ka mefuta e 'meli ea motheo e kopanang ho batla le ho timetsa lintho tse bakang mafu kapadintho.
Mefuta e 'meli ea mantlha ea li-leukocyte ke:
Li-phagocyte, lisele tse hlafunang lintho tse phelang tse hlaselang.
Li-lymphocyte, lisele tse lumellang 'mele ho hopola le ho lemoha bahlaseli ba pele le ho thusa'mele oa li timetsa.
Lisele tse 'maloa tse fapaneng li nkoa e le li-phagocyte. Mofuta o tloaelehileng haholo ke neutrophil,e loantšang baktheria haholo-holo. Haeba lingaka li tšoenyehile ka tšoaetso ea baktheria, li ka 'na tsa laelatlhahlobo ea mali ho bona hore na mokuli o na le palo e eketsehileng ea li-neutrophils tse bakoang ke tšoaetso.
Mefuta e meng ea li-phagocyte e na le mesebetsi ea eona ea ho netefatsa hore 'mele o arabela ka nepoho mofuta o itseng oa mohlaseli.
Mefuta e 'meli ea li-lymphocyte ke li-lymphocyte tsa B le li-lymphocyte tsa T. Li-lymphocyte lia qalaka mokong oa masapo 'me li lula moo ebe li hola hore e be lisele tsa B, kapa lia tloha bakeng sa thymusgland, moo li holang ho ba lisele tsa T. Li-lymphocyte tsa B le li-lymphocyte tsa T li arohanemesebetsi: Li-lymphocyte tsa B li tšoana le tsamaiso ea bohlale ba sesole sa 'mele, li batla tsa tsonalipheo le ho romela litšireletso ho li notlela. Lisele tsa T li tšoana le masole, li senyabahlaseli bao tsamaiso ea bohlale e ba hlwaileng.
Theknoloji ea sele ea T ea Chimeric antigen receptor (CAR): ke mofuta oa sele e amohelangKalafo ea 'mele ea ho itšireletsa mafung (ACI). Lisele tsa T tsa mokuli li hlahisa CAR ka ho tsosolosa liphatsa tsa lefutsotheknoloji, e etsang hore lisele tsa T tse sebetsang li shebane haholoanyane, li bolaee ebile lia phehella ho fetalisele tse tloaelehileng tsa 'mele oa ho itšireletsa mafung, 'me li ka hlōla tikoloho e nyenyane ea ho thibela sesole sa' mele ea sebakeng seo eaHo mamella 'mele oa ho itšireletsa mafung ka hlahala le ho roba. Ena ke phekolo e khethehileng ea lisele tsa 'mele tsa ho itšireletsa mafung.
Molao-motheo oa CART ke ho tlosa "mofuta o tloaelehileng" oa lisele tsa T tsa 'mele oa mokuli.le ho tswela pele ka boenjiniere ba liphatsa tsa lefutso, ho bokella ka vitro bakeng sa lipheo tse ikhethang tsa hlahala tse kholosebetsa sa antipersonnel "chimeric antigen receptor (CAR)", ebe se kenya lisele tsa T tse fetotsoengha li khutlela 'meleng oa mokuli, li-receptor tse ncha tse fetotsoeng tsa lisele li tla tšoana le ho kenya sistimi ea radar,e khonang ho tataisa lisele tsa T ho fumana le ho senya lisele tsa kankere.
Molemo oa CART ho BPIH
Ka lebaka la dipharologanyo tse teng sebopehong sa letshwao la ka hare ho sele, CAR e ntsheditse pele tse nnemeloko. Re sebelisa CART ea moloko oa morao-rao.
1stmoloko: Ho ne ho e-na le karolo e le 'ngoe feela ea lets'oao la ka hare ho sele le thibelo ea hlahalaphello e ne e le mpe.
2ndmoloko: Ho ekelitsoe molek'hule e susumetsang hammoho motheong oa moloko oa pele, 'meBokhoni 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 hlahalaHo ata le ho khothalletsa apoptosis ho ntlafetse haholo.
4thmoloko: Lisele tsa CAR-T li ka ameha ho tloseng palo ea lisele tsa hlahala kaho kenya tshebetsong karolo e ka tlase ya transcription factor NFAT ho hlahisa interleukin-12 kamora CARe lemoha antigen e reretsoeng.
| Moloko | Ho hlohlelletsa Ntlha | Tšobotsi |
| 1st | CD3ζ | Ho kenngwa tshebetsong ha disele tsa T tse ikgethang, disele tsa T tse nang le chefo, empa di ne di sa kgone ho ata le ho phela ka hare ho mmele. |
| 2nd | CD3ζ+CD28/4-1BB/OX40 | Kenya costimulator, ntlafatsa chefo ea lisele, bokhoni bo fokolang ba ho ata. |
| 3rd | CD3ζ+CD28/4-1BB/OX40+CD134/CD137 | Kenya li-costimulator tse 2, ntlafatsabokhoni ba ho ata le chefo. |
| 4th | Lefutso la ho ipolaea/Amored CAR-T (12IL) Go CAR-T | Kopanya jini ea ho ipolaea, ntlha ea 'mele ea ho itšireletsa mafung e hlahelletseng le mehato e meng e nepahetseng ea taolo. |
Mokhoa oa phekolo
1) Ho aroloa ha lisele tse tšoeu tsa mali: Lisele tsa T tsa mokuli li aroloa ho tsoa 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 kee sebediswa ho kenya tshebetsong disele tsa T.
3) Phetoho: Lisele tsa T li entsoe ka liphatsa tsa lefutso ho hlahisa CAR ka ntle ho 'mele.
4) Ho atolosoa ha lisele: Lisele tsa T tse fetotsoeng liphatsa tsa lefutso lia atolosoa ka hare ho 'mele.
5) Kalafo ea Chemotherapy: Mokuli o phekoloa esale pele ka chemotherapy pele ho kenngoa lisele tsa T hape.
6) Ho kenngoa hape: Lisele tsa T tse fetotsoeng liphatsa tsa lefutso li khutlela ho mokuli.
Matšoao
Matšoao a CAR-T
Tsamaiso ea ho hema: Kankere ea matšoafo (Kankere ea sele e nyane, kankere ea sele e nyane,adenocarcinoma), kankere ea nasopharynx, jj.
Sistimi ea tšilo ea lijo: Kankere ea sebete, ea mpa le ea mala a maholo, jj.
Tsamaiso ea moroto: Kankere ea liphio le adrenal le kankere ea metastatic, jj.
Sistimi ea mali: Leukemia ea lymphoblastic e matla le e sa foleng (T lymphoma)ha e kenyelletsoe) jj.
Kankere e 'ngoe: Kankere e kotsi ea melanoma, kankere ea matsoele, ea prostate le ea leleme, jj.
Ho buuoa ho tlosa seso sa mantlha, empa sesole sa 'mele se fokola, 'me phekolo e lieha.
Lihlahala tse nang le metastasis e pharalletseng tse neng li sa khone ho tsoela pele ka opereishene.
Litlamorao tsa chemotherapy le radiotherapy li kholo kapa ha li amehe chemotherapy le radiotherapy.
Thibela ho ipheta ha hlahala ka mora opereishene, chemotherapy le radiotherapy.
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.