Iyini i-CAR-T (i-Chimeric Antigen Receptor T-cell)?
Okokuqala, ake sibheke isimiso somzimba sokuzivikela somzimba womuntu.
Uhlelo lokuzivikela komzimba lwakhiwe yinethiwekhi yamangqamuzana, izicubu, kanye nezitho zomzimba ezisebenzisana ukuvikela umzimba. Elinye lamangqamuzana abalulekile ahilelekile amaseli amhlophe egazi, abizwa nangokuthi ama-leukocyte, afika ngezinhlobo ezimbili eziyisisekelo ezihlangana ukufuna nokubhubhisa izinto eziphilayo noma izinto ezibangela izifo.
Izinhlobo ezimbili eziyisisekelo zama-leukocyte yilezi:
Ama-phagocyte, amaseli ahlafuna izinto eziphilayo ezihlaselayo
Ama-lymphocyte, amaseli avumela umzimba ukuthi ukhumbule futhi uqaphele abahlaseli bangaphambilini futhi usize umzimba ukubabhubhisa
Amaseli amaningana ahlukene abhekwa njengama-phagocyte. Uhlobo oluvame kakhulu yi-neutrophil, elwa kakhulu namagciwane. Uma odokotela bekhathazekile ngokutheleleka ngamagciwane, bangase bacele ukuhlolwa kwegazi ukuze babone ukuthi isiguli sinenani elandayo lama-neutrophil abangelwa ukutheleleka. Ezinye izinhlobo zama-phagocyte zinemisebenzi yazo ukuqinisekisa ukuthi umzimba usabela ngendlela efanele ohlotsheni oluthile lomhlaseli.
Izinhlobo ezimbili zama-lymphocyte yi-B lymphocytes kanye nama-T lymphocytes. Ama-lymphocyte aqala emnkantsheni wethambo bese ehlala lapho bese ekhula abe amaseli e-B, noma asuke aye e-thymus gland, lapho ekhula khona abe amaseli e-T. Ama-B lymphocyte kanye nama-T lymphocyte anemisebenzi ehlukene: Ama-B lymphocyte afana nohlelo lobuhlakani bezempi lomzimba, afuna izinhloso zawo futhi athumele izivikelo ukuze ziwavale. Ama-T cell afana namasosha, abhubhisa abahlaseli uhlelo lobuhlakani olubabonile.
Uhlelo lokuzivikela komzimba lwakhiwe yinethiwekhi yamangqamuzana, izicubu, kanye nezitho zomzimba ezisebenzisana ukuvikela umzimba. Elinye lamangqamuzana abalulekile ahilelekile amaseli amhlophe egazi, abizwa nangokuthi ama-leukocyte, afika ngezinhlobo ezimbili eziyisisekelo ezihlangana ukufuna nokubhubhisa izinto eziphilayo noma izinto ezibangela izifo.
Izinhlobo ezimbili eziyisisekelo zama-leukocyte yilezi:
Ama-phagocyte, amaseli ahlafuna izinto eziphilayo ezihlaselayo
Ama-lymphocyte, amaseli avumela umzimba ukuthi ukhumbule futhi uqaphele abahlaseli bangaphambilini futhi usize umzimba ukubabhubhisa
Amaseli amaningana ahlukene abhekwa njengama-phagocyte. Uhlobo oluvame kakhulu yi-neutrophil, elwa kakhulu namagciwane. Uma odokotela bekhathazekile ngokutheleleka ngamagciwane, bangase bacele ukuhlolwa kwegazi ukuze babone ukuthi isiguli sinenani elandayo lama-neutrophil abangelwa ukutheleleka. Ezinye izinhlobo zama-phagocyte zinemisebenzi yazo ukuqinisekisa ukuthi umzimba usabela ngendlela efanele ohlotsheni oluthile lomhlaseli.
Izinhlobo ezimbili zama-lymphocyte yi-B lymphocytes kanye nama-T lymphocytes. Ama-lymphocyte aqala emnkantsheni wethambo bese ehlala lapho bese ekhula abe amaseli e-B, noma asuke aye e-thymus gland, lapho ekhula khona abe amaseli e-T. Ama-B lymphocyte kanye nama-T lymphocyte anemisebenzi ehlukene: Ama-B lymphocyte afana nohlelo lobuhlakani bezempi lomzimba, afuna izinhloso zawo futhi athumele izivikelo ukuze ziwavale. Ama-T cell afana namasosha, abhubhisa abahlaseli uhlelo lobuhlakani olubabonile.
Ubuchwepheshe be-T cell ye-Chimeric antigen receptor (CAR): uhlobo lokwelashwa nge-immunotherapy yamaseli okwamukelayo (ACI). I-T cell yesiguli iveza i-CAR ngobuchwepheshe bokwakha kabusha izakhi zofuzo, okwenza ama-T cell asebenzayo aqondiswe kakhulu, abulale futhi aqhubeke kunamaseli omzimba avamile, futhi anganqoba indawo encane yokucindezela amasosha omzimba yesimila futhi aphule ukubekezelelana kwamasosha omzimba. Lokhu kuyindlela ethile yokwelapha i-immune cell anti-tumor.
Isimiso se-CART ukukhipha "inguqulo evamile" yamaseli e-T omzimba esiguli bese uqhubeka nobunjiniyela bezakhi zofuzo, ukuhlanganisa i-in vitro ukuze kutholakale izisulu ezithile zesikhali esikhulu se-antipersonnel "i-chimeric antigen receptor (CAR)", bese ufaka amaseli e-T ashintshiwe emzimbeni wesiguli, ama-receptor amaseli amasha ashintshiwe azofana nokufaka uhlelo lwe-radar, olukwazi ukuqondisa amaseli e-T ukuthola nokubhubhisa amaseli omdlavuza.
Inzuzo ye-CART kwa-BPIH
Ngenxa yokwehluka kwesakhiwo sesizinda sesignali yangaphakathi kweseli, i-CAR ithuthukise izizukulwane ezine. Sisebenzisa i-CART yesizukulwane sakamuva.
1i-stisizukulwane: Kwakukhona ingxenye eyodwa kuphela yesignali yangaphakathi kweseli futhi umphumela wokuvimbela isimila wawumubi.
2ndisizukulwane: Kwengezwe i-molecule evuselelayo ngokusekelwe esizukulwaneni sokuqala, futhi ikhono lamaseli e-T lokubulala izimila lathuthukiswa.
3rdisizukulwane: Ngokusekelwe esizukulwaneni sesibili se-CAR, ikhono lamaseli e-T lokuvimbela ukwanda kwesimila nokukhuthaza i-apoptosis lathuthukiswa kakhulu.
4thisizukulwane: Amaseli e-CAR-T angabandakanyeka ekususweni kwenani lamaseli esimila ngokusebenzisa i-NFAT ye-transcription factor engezansi ukuze ibangele i-interleukin-12 ngemuva kokuthi i-CAR ibone i-antigen eqondiwe.
Inqubo yokwelapha
1) Ukuhlukaniswa kwamaseli amhlophe egazi: Amaseli e-T esiguli ahlukaniswa egazini elingaphandle;
2) Ukusebenza kwamaseli e-T: ubuhlalu obunamandla (amaseli e-dendritic okwenziwa) ambozwe ngama-antibodies asetshenziswa ukwenza amaseli e-T asebenze;
Ukudluliselwa Kwegciwane: Amaseli e-T aklanywe ngofuzo ukuze aveze i-CAR ngaphandle kokusebenzisa i-ejenti.
3) Ukukhulisa: Amaseli e-T aguqulwe ngofuzo akhuliswa ngaphandle kokusebenzisa izakhi zofuzo.
4) Ukwelashwa ngamakhemikhali: Isiguli siphathwa ngamakhemikhali ngaphambi kokufakwa kabusha kwamaseli e-T;
5) Ukuphinda kufakwe: Amaseli e-T aguqulwe ngofuzo aphinde angene esigulini.
Izinzuzo:
1)Amaseli e-CAR T ahlosiwe kakhulu futhi angabulala amaseli esimila ngokuqondene ne-antigen ngempumelelo enkulu.
2)Ukwelashwa ngamaseli e-CAR-T kudinga isikhathi esincane. I-CAR T idinga isikhathi esifushane kakhulu sokukhulisa amaseli e-T ngoba idinga amaseli ambalwa ngaphansi komphumela ofanayo wokwelashwa. Umjikelezo wokukhuliswa kwe-vitro ungafinyezwa ube amasonto ama-2, okunciphisa kakhulu isikhathi sokulinda.
3)I-CAR ayikwazi ukubona ama-antigen e-peptide kuphela, kodwa futhi nama-antigen kashukela nama-lipid, yandisa ububanzi obuqondiwe bama-antigen esimila. Ukwelashwa kwe-CAR T akukhawulelwe futhi yi-protein antigens yamaseli esimila. I-CAR T ingasebenzisa ama-antigen kashukela nama-lipid angewona amaprotheni amaseli esimila ukuthola ama-antigen ngezindlela eziningi.
4)I-CAR-T inokuphindwaphindwa kwe-spectrum ebanzi. Njengoba izindawo ezithile zivezwa kumaseli amaningi esimila, njenge-EGFR, i-CAR gene yale antigen ingasetshenziswa kabanzi uma isikhiwe.
5)Amaseli e-CAR T anomsebenzi wokukhumbula amasosha omzimba futhi angaphila emzimbeni isikhathi eside. Kubaluleke kakhulu emtholampilo ukuvimbela ukuphindaphinda kwesimila.