Iyini i-CAR-T (Chimeric Antigen Receptor T-cell)?
Okokuqala, ake sibheke isimiso somzimba sokuzivikela ezifweni.
Amasosha omzimba akhiwe inethiwekhi yamangqamuzana, izicubu, nezitho ezisebenza ndawonye ukuze zivikele umzimba.Elinye lamangqamuzana abalulekile ahilelekile amangqamuzana egazi amhlophe, abizwa nangokuthi ama-leukocyte, afika ngezinhlobo ezimbili eziyisisekelo ezihlanganayo ukuze zifune futhi zibhubhise izinto eziphilayo ezidala izifo noma izinto.
Izinhlobo ezimbili eziyisisekelo zama-leukocyte ziyi:
Ø ama-phagocyte, amaseli ahlafuna izinto eziphilayo ezihlaselayo
Ø ama-lymphocyte, amaseli avumela umzimba ukuba ukhumbule futhi uqaphele abahlaseli bangaphambilini futhi asize umzimba ukuba ubabhubhise
Inani lamaseli ahlukene abhekwa njengama-phagocyte.Uhlobo oluvame kakhulu yi-neutrophil, elwa namagciwane ngokuyinhloko.Uma odokotela bekhathazekile ngokutheleleka ngebhaktheriya, bangase ba-oda ukuhlolwa kwegazi ukuze babone ukuthi isiguli sinenani elikhulayo lama-neutrophils abangelwa ukutheleleka.Ezinye izinhlobo ze-phagocyte zinemisebenzi yazo yokuqinisekisa ukuthi umzimba uphendula ngendlela efanele ohlotsheni oluthile lomhlaseli.
Izinhlobo ezimbili zama-lymphocyte yi-B lymphocytes kanye ne-T lymphocytes.Ama-lymphocyte aqala emnkantsheni futhi ahlale lapho futhi avuthwe abe amangqamuzana e-B, noma ahambe aye ku-thymus gland, lapho evuthwa khona abe ama-T cell.Ama-lymphocyte e-B nama-T lymphocyte anemisebenzi ehlukene: Ama-lymphocyte e-B afana nesistimu yezobuhlakani bezempi yomzimba, efuna izinhloso zawo futhi athumele izivikelo ukuze zikhiye kuwo.Ama-T cell afana namasosha, abhubhisa abahlaseli abahlonziwe uhlelo lwezobunhloli.
Amasosha omzimba akhiwe inethiwekhi yamangqamuzana, izicubu, nezitho ezisebenza ndawonye ukuze zivikele umzimba.Elinye lamangqamuzana abalulekile ahilelekile amangqamuzana egazi amhlophe, abizwa nangokuthi ama-leukocyte, afika ngezinhlobo ezimbili eziyisisekelo ezihlanganayo ukuze zifune futhi zibhubhise izinto eziphilayo ezidala izifo noma izinto.
Izinhlobo ezimbili eziyisisekelo zama-leukocyte ziyi:
Ø ama-phagocyte, amaseli ahlafuna izinto eziphilayo ezihlaselayo
Ø ama-lymphocyte, amaseli avumela umzimba ukuba ukhumbule futhi uqaphele abahlaseli bangaphambilini futhi asize umzimba ukuba ubabhubhise
Inani lamaseli ahlukene abhekwa njengama-phagocyte.Uhlobo oluvame kakhulu yi-neutrophil, elwa namagciwane ngokuyinhloko.Uma odokotela bekhathazekile ngokutheleleka ngebhaktheriya, bangase ba-oda ukuhlolwa kwegazi ukuze babone ukuthi isiguli sinenani elikhulayo lama-neutrophils abangelwa ukutheleleka.Ezinye izinhlobo ze-phagocyte zinemisebenzi yazo yokuqinisekisa ukuthi umzimba uphendula ngendlela efanele ohlotsheni oluthile lomhlaseli.
Izinhlobo ezimbili zama-lymphocyte yi-B lymphocytes kanye ne-T lymphocytes.Ama-lymphocyte aqala emnkantsheni futhi ahlale lapho futhi avuthwe abe amangqamuzana e-B, noma ahambe aye ku-thymus gland, lapho evuthwa khona abe ama-T cell.Ama-lymphocyte e-B nama-T lymphocyte anemisebenzi ehlukene: Ama-lymphocyte e-B afana nesistimu yezobuhlakani bezempi yomzimba, efuna izinhloso zawo futhi athumele izivikelo ukuze zikhiye kuwo.Ama-T cell afana namasosha, abhubhisa abahlaseli abahlonziwe uhlelo lwezobunhloli.
I-Chimeric antigen receptor(CAR) T cell technology: iwuhlobo lwe-adoptive cell immunotherapy(ACI).I-T cell yesiguli iveza i-CAR ngobuchwepheshe bokwakha kabusha izakhi zofuzo, okwenza ama-T cell anomthelela aqondiswe kakhulu, abulale futhi aphikelele kunamangqamuzana okuzivikela omzimba avamile, futhi anganqoba i-microenvironment immunosuppressive microenvironment yesimila futhi aphule ukubekezelelana kwamasosha omzimba.Lena i-immune cell anti-tumor therapy.
Umgomo we-CART ukukhipha “inguqulo evamile” yamaseli T esiguli omzimba futhi aqhubeke nobunjiniyela bezakhi zofuzo, ahlanganise i-vitro ukuze uthole okuqondiwe okukhethekile kwesimila sesikhali esikhulu esilwa nabasebenzi “i-chimeric antigen receptor (CAR)”, bese efaka uguquko. Ama-T cell abuyele emzimbeni wesiguli, ama-cell receptors amasha ashintshiwe azofana nokufaka uhlelo lwe-radar, olukwazi ukuqondisa ama-T cell athole futhi abhubhise amangqamuzana omdlavuza.
Inzuzo ye-CART kwa-BPIH
Ngenxa yomehluko wesakhiwo sesizinda sesignali ye-intracellular, i-CAR ithuthukise izizukulwane ezine.Sisebenzisa isizukulwane sakamuva INQALI.
1Stisizukulwane: Bekunengxenye eyodwa kuphela yesignali ye-intracellular futhi umphumela wokuvimbela isimila ubumpofu.
2ndisizukulwane: Kwengezwe i-molecule ekhuthazayo ngesisekelo sesizukulwane sokuqala, futhi amandla ama-T cell okubulala izimila athuthukiswa.
3rdisizukulwane: Ngokusekelwe esizukulwaneni sesibili se-CAR, ikhono lamaseli e-T ukuvimbela ukwanda kwesimila nokukhuthaza i-apoptosis lathuthukiswa kakhulu.
4thisizukulwane: Amaseli e-CAR-T angahileleka ekususweni kwesibalo samangqamuzana esimila ngokwenza kusebenze isici sokulotshwa esingezansi komfula i-NFAT ukuze senze i-interleukin-12 ngemva kokuba i-CAR ibone i-antigen eqondiwe.
Inqubo yokwelapha
1) Ukuhlukaniswa kwamangqamuzana amhlophe egazi: Ama-T cell esiguli ahlukanisiwe negazi le-peripheral;
I-2) Ukusebenza kwama-T cell: ubuhlalu kazibuthe (amangqamuzana e-dendritic okwenziwa) ahlanganiswe namasosha omzimba asetshenziselwa ukwenza amaseli e-T asebenze;
Ukudluliselwa: Amaseli e-T akhiwe ngofuzo ukuze aveze i-CAR in vitro.
3) Ukukhulisa: Amaseli e-T aguqulwe ngofuzo akhuliswa nge-vitro.
I-4) I-Chemotherapy: Isiguli selashwa kusengaphambili nge-chemotherapy ngaphambi kokubuyiselwa kwe-T cell;
I-5) Ukufakwa kabusha: Amaseli e-T ashintshwe izakhi abuyisela esigulini.
Izinzuzo:
1)Amaseli e-CAR T aqondiswe kakhulu futhi angabulala amaseli wesimila ane-antigen eqondile ngokuphumelelayo.
2)Ukwelashwa kwamaseli e-CAR-T kudinga isikhathi esincane.I-CAR T idinga isikhathi esifushane kakhulu kumaseli T e-culture ngoba idinga amaseli ambalwa ngaphansi komphumela ofanayo wokwelapha.Umjikelezo we-vitro culture ungafinyezwa ube amaviki ama-2, okunciphise kakhulu isikhathi sokulinda.
3)I-CAR ayikwazi ukubona kuphela ama-antigen e-peptide, kodwa futhi ushukela nama-lipid antigens, yandisa uhla oluhlosiwe lwama-antigens wesimila.Ukwelashwa kwe-CAR T nakho akukhawulelwe ngama-protein antigens amaseli esimila.I-CAR T ingasebenzisa ama-antigens ashukela kanye ne-lipid angewona amaprotheni amaseli wesimila ukuze ahlonze ama-antigen ngezilinganiso eziningi.
4)I-CAR-T inobubanzi obuthile - ukukhiqiza kabusha kwe-spectrum.Njengoba izingosi ezithile zivezwa ngamaseli amaningi wesimila, njenge-EGFR, isakhi sofuzo seCAR sale antigen singasetshenziswa kabanzi uma sesakhiwe.
5)Amaseli e-CAR T anenkumbulo yokusebenza komzimba futhi angaphila isikhathi eside emzimbeni.Kubaluleke kakhulu emtholampilo ukuvimbela ukuphindeka kwesimila.