He aha ka CAR-T (Chimeric Antigen Receptor T-cell)?
ʻO ka mea mua, e nānā kākou i ka ʻōnaehana pale o ke kanaka.
Ua hana ʻia ka ʻōnaehana pale ma o kahi pūnaewele o nā pūnaewele, nā ʻiʻo, a me nā ʻōkana e hana pū ana e pale i ke kino. ʻO kekahi o nā pūnaewele koʻikoʻi e pili ana, ʻo ia nā pūnaewele koko keʻokeʻo, i kapa ʻia hoʻi he leukocytes, i hele mai i ʻelua mau ʻano kumu e hui pū ana e ʻimi a luku i nā meaola a i ʻole nā mea e hoʻoulu ai i ka maʻi.
ʻElua mau ʻano nui o nā leukocytes:
Ø nā phagocytes, nā pūnaewele e nau ana i nā meaola hoʻouka kaua
ʻO nā lymphocytes Ø, nā pūnaewele e ʻae i ke kino e hoʻomanaʻo a ʻike i nā mea hoʻouka mua a kōkua i ke kino e luku iā lākou
Ua manaʻo ʻia he nui nā ʻano pūnaewele like ʻole he phagocytes. ʻO ke ʻano maʻamau ka neutrophil, ka mea e hakakā nui ai i ka bacteria. Inā hopohopo nā kauka e pili ana i kahi maʻi bacteria, e kauoha paha lākou i kahi hoʻāʻo koko e ʻike inā loaʻa i kahi maʻi ka nui o nā neutrophils i hoʻoulu ʻia e ka maʻi. Loaʻa i nā ʻano phagocytes ʻē aʻe kā lākou hana ponoʻī e hōʻoia i ka pane kūpono ʻana o ke kino i kahi ʻano kikoʻī o ka mea hoʻouka.
ʻO nā ʻano lymphocytes ʻelua he mau lymphocytes B a me nā lymphocytes T. Hoʻomaka nā lymphocytes i loko o ka iwi iwi a noho ma laila a oʻo i loko o nā pūnaewele B, a i ʻole e haʻalele lākou no ka gland thymus, kahi e oʻo ai i loko o nā pūnaewele T. He mau hana kaʻawale ko nā lymphocytes B a me nā lymphocytes T: Ua like nā lymphocytes B me ka ʻōnaehana akamai koa o ke kino, e ʻimi ana i kā lākou mau pahuhopu a hoʻouna i nā pale e laka iā lākou. Ua like nā pūnaewele T me nā koa, e luku ana i nā mea hoʻouka kaua i ʻike ʻia e ka ʻōnaehana akamai.
Ua hana ʻia ka ʻōnaehana pale ma o kahi pūnaewele o nā pūnaewele, nā ʻiʻo, a me nā ʻōkana e hana pū ana e pale i ke kino. ʻO kekahi o nā pūnaewele koʻikoʻi e pili ana, ʻo ia nā pūnaewele koko keʻokeʻo, i kapa ʻia hoʻi he leukocytes, i hele mai i ʻelua mau ʻano kumu e hui pū ana e ʻimi a luku i nā meaola a i ʻole nā mea e hoʻoulu ai i ka maʻi.
ʻElua mau ʻano nui o nā leukocytes:
Ø nā phagocytes, nā pūnaewele e nau ana i nā meaola hoʻouka kaua
ʻO nā lymphocytes Ø, nā pūnaewele e ʻae i ke kino e hoʻomanaʻo a ʻike i nā mea hoʻouka mua a kōkua i ke kino e luku iā lākou
Ua manaʻo ʻia he nui nā ʻano pūnaewele like ʻole he phagocytes. ʻO ke ʻano maʻamau ka neutrophil, ka mea e hakakā nui ai i ka bacteria. Inā hopohopo nā kauka e pili ana i kahi maʻi bacteria, e kauoha paha lākou i kahi hoʻāʻo koko e ʻike inā loaʻa i kahi maʻi ka nui o nā neutrophils i hoʻoulu ʻia e ka maʻi. Loaʻa i nā ʻano phagocytes ʻē aʻe kā lākou hana ponoʻī e hōʻoia i ka pane kūpono ʻana o ke kino i kahi ʻano kikoʻī o ka mea hoʻouka.
ʻO nā ʻano lymphocytes ʻelua he mau lymphocytes B a me nā lymphocytes T. Hoʻomaka nā lymphocytes i loko o ka iwi iwi a noho ma laila a oʻo i loko o nā pūnaewele B, a i ʻole e haʻalele lākou no ka gland thymus, kahi e oʻo ai i loko o nā pūnaewele T. He mau hana kaʻawale ko nā lymphocytes B a me nā lymphocytes T: Ua like nā lymphocytes B me ka ʻōnaehana akamai koa o ke kino, e ʻimi ana i kā lākou mau pahuhopu a hoʻouna i nā pale e laka iā lākou. Ua like nā pūnaewele T me nā koa, e luku ana i nā mea hoʻouka kaua i ʻike ʻia e ka ʻōnaehana akamai.
ʻO ka ʻenehana cell T Chimeric antigen receptor (CAR): he ʻano immunotherapy cellular adoptive (ACI). Hōʻike ka cell T o ka mea maʻi iā CAR ma o ka ʻenehana hana hou genetic, ka mea e ʻoi aku ka kikoʻī o nā cell effector T, make a mau loa ma mua o nā cell immune maʻamau, a hiki ke lanakila i ka microenvironment immunosuppressive kūloko o ka tumor a uhaki i ka hoʻomanawanui o ka immune host. He lāʻau lapaʻau anti-tumor kikoʻī kēia no nā cell immune.
ʻO ke kumumanaʻo o CART, ʻo ia ke lawe ʻana i ka "mana maʻamau" o nā pūnaewele T pale ponoʻī o ka mea maʻi a hoʻomau i ka ʻenekinia gene, e hōʻuluʻulu i loko o ka vitro no nā pahuhopu kikoʻī o ka tumor o ka mea kaua antipersonnel nui "chimeric antigen receptor (CAR)", a laila e hoʻokomo hou i nā pūnaewele T i hoʻololi ʻia i loko o ke kino o ka mea maʻi, e like me ka hoʻokomo ʻana i kahi ʻōnaehana radar nā mea loaʻa pūnaewele hou i hoʻololi ʻia, hiki ke alakaʻi i nā pūnaewele T e ʻimi a luku i nā pūnaewele kanesa.
ʻO ka pono o CART ma BPIH
Ma muli o nā ʻokoʻa o ke ʻano o ka ʻāpana hōʻailona intracellular, ua hoʻomohala ʻo CAR i ʻehā mau hanauna. Hoʻohana mākou i ka hanauna hou loa ʻo CART.
1sthanauna: Hoʻokahi wale nō ʻāpana hōʻailona intracellular a ʻaʻole maikaʻi ka hopena pale ʻana o ka maʻi ʻōpū.
2ndhanauna: Ua hoʻohui ʻia kahi molekala hoʻouluulu like ma ke kumu o ka hanauna mua, a ua hoʻomaikaʻi ʻia ka hiki o nā pūnaewele T ke pepehi i nā ʻōpū.
3rdhanauna: Ma muli o ka lua o ka hanauna o CAR, ua hoʻomaikaʻi nui ʻia ka hiki o nā pūnaewele T ke kāohi i ka hoʻonui ʻana o ka maʻi ʻōpū a hoʻolaha i ka apoptosis.
4thhanauna: Hiki i nā pūnaewele CAR-T ke komo i ka hoʻomaʻemaʻe ʻana o ka heluna o nā pūnaewele tumor ma o ka hoʻoulu ʻana i ka downstream transcription factor NFAT e hoʻoulu i ka interleukin-12 ma hope o ka ʻike ʻana o CAR i ka antigen target.
Kaʻina hana lapaʻau
1) Hoʻokaʻawale ʻana i nā hunaola koko keʻokeʻo: Hoʻokaʻawale ʻia nā hunaola T o ka mea maʻi mai ke koko peripheral;
2) Hoʻoulu ʻana o nā pūnaewele T: hoʻohana ʻia nā momi magnetic (nā pūnaewele dendritic artificial) i uhi ʻia me nā antibodies e hoʻoulu i nā pūnaewele T;
Hoʻololi ʻana: Ua hana ʻia nā pūnaewele T ma ke ʻano genetic e hōʻike i ka CAR in vitro.
3) Hoʻonui: Hoʻonui ʻia nā pūnaewele T i hoʻololi ʻia i ka genetics in vitro.
4) Chemotherapy: Hoʻomaʻamaʻa mua ʻia ka mea maʻi me ka chemotherapy ma mua o ka hoʻokomo hou ʻana o nā cell T;
5) Hoʻokomo hou ʻia: Hoʻokomo hou nā pūnaewele T i hoʻololi ʻia i ka genetics i loko o ka mea maʻi.
Nā Pōmaikaʻi:
1)Hoʻopaʻa nui ʻia nā pūnaewele CAR T a hiki ke pepehi i nā pūnaewele tumor me ke ʻano kūikawā o ka antigen me ka ʻoi aku ka maikaʻi.
2)ʻOi aku ka liʻiliʻi o ka manawa e pono ai ka lāʻau lapaʻau CAR-T. ʻOi aku ka pōkole o ka manawa e pono ai ʻo CAR T e hoʻoulu i nā cell T no ka mea ʻoi aku ka liʻiliʻi o nā cell e pono ai ma lalo o ka hopena lapaʻau like. Hiki ke hoʻopōkole ʻia ke kaʻina hana vitro i 2 mau pule, kahi i hoʻemi nui ai i ka manawa kali.
3)Hiki iā CAR ke ʻike ʻaʻole wale i nā antigens peptide, akā, i nā antigens kō a me lipid, e hoʻonui ana i ka laulā o nā antigens tumor. ʻAʻole i kaupalena ʻia ka lāʻau lapaʻau CAR T e nā antigens protein o nā cell tumor. Hiki iā CAR T ke hoʻohana i nā antigens non-protein kō a me lipid o nā cell tumor e ʻike i nā antigens i nā ana he nui.
4)Loaʻa iā CAR-T kahi ʻano hana hou ākea. ʻOiai ua hōʻike ʻia kekahi mau wahi i loko o nā cell tumor he nui, e like me EGFR, hiki ke hoʻohana nui ʻia kahi gene CAR no kēia antigen ke kūkulu ʻia.
5)Loaʻa i nā pūnaewele CAR T ka hana hoʻomanaʻo palekana a hiki ke ola i loko o ke kino no ka manawa lōʻihi. He mea koʻikoʻi nui ia no ka pale ʻana i ka hoʻi hou ʻana o ka puʻupuʻu.