Iyini i-CAR-T (Chimeric Antigen Receptor T-cell)?
Okokuqala, ake sibheke isimiso somzimba sokuzivikela ezifweni.
Amasosha omzimba akhiwe inethiwekhi yamaseli, izicubu, nezitho ezisebenza ndawonyevikela umzimba.Elinye lamangqamuzana abalulekile ahilelekile amangqamuzana amhlophe egazi, abizwa nangokuthi ama-leukocyte,ezifika ngezinhlobo ezimbili eziyisisekelo ezihlanganayo ukufuna nokucekela phansi izinto eziphilayo ezibanga izifo nomaizinto.
Izinhlobo ezimbili eziyisisekelo zama-leukocyte ziyi:
Ama-phagocyte, amangqamuzana ahlafuna izinto eziphilayo ezihlaselayo.
Ama-Lymphocyte, amaseli avumela umzimba ukuba ukhumbule futhi uqaphele abahlaseli bangaphambilini nokusizaumzimba ubabhubhise.
Inani lamaseli ahlukene abhekwa njengama-phagocyte.Uhlobo oluvame kakhulu yi-neutrophil,okuyinto ngokuyinhloko elwa namagciwane.Uma odokotela bekhathazekile ngokutheleleka kwebhaktheriya, bangase ba-odaukuhlolwa kwegazi ukuze kubonakale ukuthi isiguli sinalo yini inani elandiwe lama-neutrophils abangelwa ukutheleleka.
Ezinye izinhlobo ze-phagocyte zinemisebenzi yazo yokuqinisekisa ukuthi umzimba uphendula ngendlela efaneleohlotsheni oluthile lomhlaseli.
Izinhlobo ezimbili zama-lymphocyte yi-B lymphocytes kanye ne-T lymphocytes.I-Lymphocyte iqalaemnkantsheni futhi ahlale lapho futhi avuthwe abe amaseli B, noma ahambe aye ku-thymusindlala, lapho zivuthwa khona zibe ama-T cell.Ama-lymphocyte e-B nama-T lymphocyte ahlukeneimisebenzi: B lymphocyte zifana nesimiso somzimba wezempi intelligence, efuna kwabookuhlosiwe kanye nokuthumela izivikelo ukuze ukhiye kuzo.Ama-T cell afana namasosha, abhubhisaabahlaseli abahlonzwe uhlelo lwezobunhloli.
I-Chimeric antigen receptor(CAR) T cell technology: iwuhlobo lwamaselula owamukelayoi-immunotherapy (ACI).I-T cell yesiguli iveza i-CAR ngokwakhiwa kabusha kofuzoubuchwepheshe, okwenza ama-T cell asebenzayo aqondiswe kakhulu, abulale futhi aqhubekeamangqamuzana omzimba ezivamile, futhi anganqoba wendawo immunosuppressive microenvironment ofi-tumor kanye ne-break host immune tolerance.Lena i-immune cell anti - tumor therapy ethize.
Umgomo we-CART uwukukhipha "inguqulo evamile" yama-T cell esigulifuthi uqhubeke nobunjiniyela bezakhi zofuzo, hlanganisa i-in vitro ngezinhloso ezithile zesimila ezinkuluIsikhali se-antipersonnel "chimeric antigen receptor (CAR)", bese sifaka amaseli e-T ashintshileemuva emzimbeni wesiguli, ama-cell receptors amasha ashintshiwe azofana nokufaka uhlelo lwe-radar,ekwazi ukuqondisa ama-T cell athole futhi abhubhise amangqamuzana omdlavuza.
Inzuzo ye-CART kwa-BPIH
Ngenxa yomehluko wesakhiwo sesizinda sesignali ye-intracellular, i-CAR ithuthukise ezineizizukulwane.Sisebenzisa isizukulwane sakamuva INQALI.
1stisizukulwane: Kwakunengxenye eyodwa kuphela yesignali ye-intracellular kanye nokuvimbela isimilaumphumela wawungemuhle.
2ndisizukulwane: Kwengezwe i-molecule ekhuthazayo ngesisekelo sesizukulwane sokuqala, kanye ne-amandla ama-T cell okubulala izimila aba ngcono.
3rdisizukulwane: Ngokusekelwe esizukulwaneni sesibili se-CAR, ikhono lama-T cell ukuvimbela isimilaukwanda nokukhuthaza i-apoptosis kwathuthukiswa kakhulu.
4thisizukulwane: Amaseli e-CAR-T angabandakanyeka ekususweni kwesibalo samaseli e-tumor byivula isici sokuloba esingezansi somfula i-NFAT ukuze kusetshenziswe i-interleukin-12 ngemva kwe-CARibona i-antigen eqondiwe.
| Isizukulwane | Ukukhuthazwa Isici | Isici |
| 1st | CD3ζ | Ukwenziwa kusebenze kwe-T cell, i-cytotoxic T cell, kodwa ayikwazanga ukwanda nokuphila ngaphakathi komzimba. |
| 2nd | I-CD3ζ+CD28/4-1BB/OX40 | Engeza i-costimulator, thuthukisa ubuthi beseli, ikhono elilinganiselwe lokwanda. |
| 3rd | CD3ζ+CD28/4-1BB/OX40+CD134 /CD137 | Engeza ama-costimulators angu-2, ngconoikhono lokwanda nobuthi. |
| 4th | Ufuzo lokuzibulala/I-Amored CAR-T (12IL) Hamba CAR-T | Hlanganisa isakhi sofuzo sokuzibulala, veza isici sokuzivikela ezifweni nezinye izinyathelo zokulawula ezinembayo. |
Inqubo yokwelapha
I-1) Ukuhlukaniswa kwamangqamuzana egazi amhlophe: Ama-T cell esiguli ahlukanisiwe negazi le-peripheral.
2) Ukwenziwa kusebenze kwamaseli e-T: ubuhlalu kazibuthe (amaseli e-dendritic okwenziwa) ambozwe amasosha omzimbaasetshenziselwa ukwenza ama-T cell asebenze.
I-3) Ukudluliselwa: Amaseli e-T akhiwe ngofuzo ukuze aveze i-CAR in vitro.
4) Ukukhulisa: Amaseli e-T aguqulwe ngofuzo akhuliswa nge-vitro.
I-5) I-Chemotherapy: Isiguli selashwa ngaphambilini nge-chemotherapy ngaphambi kokufakwa kabusha kwe-T cell.
I-6) Ukufakwa kabusha: Amaseli e-T ashintshwe izakhi abuyisela esigulini.
Izinkomba
Izinkomba ze-CAR-T
Uhlelo lokuphefumula: Umdlavuza wamaphaphu (Small cell carcinoma, squamous cell carcinoma,i-adenocarcinoma), umdlavuza we-nasopharynx, njll.
Uhlelo lokugaya ukudla: Isibindi, isisu kanye nomdlavuza we-colorectal, njll.
Uhlelo lomchamo: Izinso kanye ne-adrenal carcinoma kanye ne-metastatic cnacer, njll.
Uhlelo lwegazi: I-acute and chronic lymphoblastic leukemia (T lymphomaokungafakiwe) njll.
Omunye umdlavuza: I-Malignant melanoma, ibele, i-prostae nomdlavuza wolimi, njll.
Ukuhlinzwa ukuze kukhishwe isilonda esiyinhloko, kodwa ukungavikeleki kuphansi, futhi ukululama kuhamba kancane.
Amathumba ane-metastasis esabalele angakwazanga ukuqhubeka nokuhlinzwa.
Umthelela oseceleni we-chemotherapy kanye ne-radiotherapy mkhulu noma awuzweli ku-chemotherapy kanye ne-radiotherapy.
Vimbela ukuphindaphinda kwesimila ngemva kokuhlinzwa, i-chemotherapy kanye ne-radiotherapy.
Izinzuzo
I-1) Amaseli e-CAR T aqondiswe kakhulu futhi angabulala amaseli wesimila ane-antigen ecacile ngokuphumelelayo.
2) Ukwelashwa kwe-CAR-T cell 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.
I-3) I-CAR ayikwazi ukubona ama-antigens e-peptide kuphela, kodwa futhi noshukela nama-antigens e-lipid, yandisa uhla oluhlosiwe lwe-tumor antigens.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.
I-5) Amaseli e-CAR T anenkumbulo yokusebenza komzimba futhi angaphila emzimbeni isikhathi eside.Kubaluleke kakhulu emtholampilo ukuvimbela ukuphindeka kwesimila.