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 hosireletsa mmele.E 'ngoe ea lisele tsa bohlokoa tse amehang ke lisele tse tšoeu tsa mali, tseo hape li bitsoang leukocyte,tse tlang ka mefuta e mmedi ya motheo e kopanang ho batla le ho timetsa dikokwanyana tse bakang mafu kapadintho.
Mefuta e 'meli ea mantlha ea leukocyte ke:
Li-phagocyte, lisele tse hlafunang likokoana-hloko tse hlaselang.
Li-lymphocyte, lisele tse lumellang 'mele ho hopola le ho lemoha bahlaseli ba pele le thuso'mele oa li 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 laelateko 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 hantleho mofuta o itseng wa mohlaseli.
Mefuta e 'meli ea li-lymphocyte ke B lymphocyte le T lymphocyte.Li-lymphocyte lia qalamokong oa masapo 'me e ka lula moo ebe e hola ho ba lisele tsa B, kapa li tloha ho ea thymusgland, moo li hōlang ho ba T lisele.Li-lymphocyte tsa B le T lymphocyte li arohanemesebetsi: Li-lymphocyte tsa B li tšoana le tsamaiso ea 'mele ea sesole sa sesole, e batla ho tsebaliphofu le ho romela litšireletso ho notlela holim'a tsona.Lisele tsa T li tšoana le masole a senyangbahlaseli bao tsamaiso ea bohlale e ba khethileng.
Chimeric antigen receptor(CAR) T cell technology: ke mofuta oa lisele tse amohelangimmunotherapy (ACI).T cell ea mokuli e hlahisa CAR ka ho nchafatsa liphatsa tsa lefutsothekenoloji, e etsang hore lisele tsa T tsa phello li lebisitsoe ho feta, tse bolaeang le tse phehellang ho fetalisele tse tloaelehileng tsa 'mele oa ho itšireletsa mafung,' me a ka hlōla sebakeng seo immunosuppressive microenvironment eahlahala le break host immune mamello.Ena ke phekolo e khethehileng ea lisele tsa 'mele ea ho itšireletsa mafung.
Molao-motheo oa CART ke ho ntša "mofuta o tloaelehileng" oa lisele tsa T tsa 'mele tsa mokuli'me u tsoele pele ka boenjiniere ba liphatsa tsa lefutso, u bokelle in vitro bakeng sa sepheo sa tumor se seholosebetsa sa antipersonnel "chimeric antigen receptor (CAR)", ebe se kenya lisele tsa T tse fetotsoeng.ho 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 kankere.
Molemo oa CART ho BPIH
Ka lebaka la ho se tšoane ha sebopeho sa sebaka sa matšoao a intracellular, CAR e hlahisitse tse 'nemeloko.Re sebelisa CART ea morao-rao ea moloko.
1stmoloko: Ho ne ho e-na le karolo e le 'ngoe feela ea matšoao a intracellular le thibelo ea tumorphello e ne e fokola.
2ndmoloko: E kentse molek'hule e kopanyang motheong oa moloko oa pele, le hobokhoni ba lisele tsa T ho bolaea lihlahala bo ile ba ntlafala.
3rdmoloko: Ho itšetlehile ka moloko oa bobeli oa CAR, bokhoni ba lisele tsa T ho thibela hlahalaho ata le ho khothaletsa apoptosis ho ile ha ntlafala haholo.
4thmoloko: Lisele tsa CAR-T li ka kenya letsoho ho hlakoloeng ha baahi ba lisele tsa tumor kaho kenya tšebetsong ntlha e tlase ea mongolo oa NFAT ho kenya interleukin-12 kamora CARe lemoha antigen e lebisitsoeng.
| Moloko | Khothatso Ntlha | Sebopeho |
| 1st | CD3ζ | Tšebeliso e khethehileng ea T cell, cytotoxic T cell, empa e ne e sitoa ho ata le ho phela ka hare ho 'mele. |
| 2nd | CD3ζ+CD28/4-1BB/OX40 | Eketsa costimulator, ntlafatsa chefo ea lisele, bokhoni bo fokolang ba ho ata. |
| 3rd | CD3ζ+CD28/4-1BB/OX40+CD134 /CD137 | Kenya li-costimulators tse 2, ntlafatsamatla a ho ata le chefo. |
| 4th | Mofuta oa ho ipolaea/Amored CAR-T (12IL) Eya CAR-T | Kopanya lefutso la ho ipolaea, hlahisa boemo ba 'mele oa ho itšireletsa mafung le mehato e meng e nepahetseng ea ho laola. |
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.e sebelisetsoang ho kenya lisele tsa T tšebetsong.
3) Phetoho: Lisele tsa T li entsoe ka liphatsa tsa lefutso ho hlahisa CAR in vitro.
4) Amplification: Lisele tsa T tse fetotsoeng ka liphatsa tsa lefutso li holisoa ka in vitro.
5) Chemotherapy: Mokuli o phekoloa ka chemotherapy pele ho T cell reinfusion.
6) Ho tšeloa hape: Lisele tsa T tse fetotsoeng ka liphatsa tsa lefutso li khutlisetsa ho mokuli.
Lipontšo
Lipontšo tsa CAR-T
Sistimi ea ho hema: Kankere ea matšoafo (Small cell carcinoma, squamous cell carcinoma,adenocarcinoma), kankere ea nasopharynx, joalo-joalo.
Sistimi ea tšilo ea lijo: Sebete, mala le mofetše oa colorectal, joalo-joalo.
Sistimi ea moroto: liphio le adrenal carcinoma le metastatic cnacer, joalo-joalo.
Sistimi ea mali: Acute and chronic lymphoblastic leukemia (T lymphomakhaotsoe) joalo-joalo.
Kankere e 'ngoe: Malignant melanoma, letsoele, prostae le mofetše oa leleme, joalo-joalo.
Ho etsoa opereishene ea ho tlosa leqeba la mantlha, empa matla a ho itšireletsa mafung a tlase, 'me ho fola hoa lieha.
Lihlahala tse nang le metastasis tse atileng tse sa khoneng ho tsoela pele ho buuoa.
Litla-morao tsa chemotherapy le radiotherapy li kholo kapa ha li utloe ho chemotherapy le radiotherapy.
Thibela ho hlaha ha hlahala ka mor'a ho buuoa, chemotherapy le radiotherapy.
Melemo
1) Lisele tsa CAR T li lebisitsoe haholo 'me li ka bolaea lisele tsa hlahala tse nang le antigen ka mokhoa o atlehileng haholoanyane.
2) Kalafo ea sele ea CAR-T e hloka nako e fokolang.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 atolosa 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 mokhoa o itseng o pharaletseng oa ho ikatisa.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.