He aha ka CAR-T (Chimeric Antigen Receptor T-cell)?
ʻO ka mea mua, e nānā kākou i ka ʻōnaehana pale o ke kanaka.
ʻO ka ʻōnaehana pale maʻi ua hana ʻia me kahi pūnaewele o nā cell, nā ʻiʻo, a me nā ʻōpū e hana pū ana epale 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 e hoʻoulu ai i ka maʻi a i ʻolenā mea hana.
ʻElua mau ʻano nui o nā leukocytes:
ʻO nā phagocytes, nā pūnaewele e nau ana i nā meaola hoʻouka kaua.
ʻO nā Lymphocytes, nā pūnaewele e ʻae i ke kino e hoʻomanaʻo a ʻike i nā mea hoʻouka mua a kōkuae luku ke kino iā lākou.
Ua manaʻo ʻia he mau phagocytes kekahi mau ʻano pūnaewele like ʻole. 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 lākouhe hoʻāʻo koko e ʻike ai inā loaʻa i ka mea maʻi kahi helu 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 kinoi kahi ʻano kikoʻī o ka mea hoʻouka kaua.
ʻO nā ʻano lymphocytes ʻelua he mau lymphocytes B a me nā lymphocytes T. Hoʻomaka nā lymphocytesi 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 thymuskelepaʻi, kahi e oʻo ai lākou i loko o nā pūnaewele T. Loaʻa i nā lymphocytes B a me nā lymphocytes T nā ʻokoʻanā hana: Ua like nā lymphocytes B me ka ʻōnaehana naʻauao koa o ke kino, e ʻimi ana i kā lākounā pahuhopu a me ka hoʻouna ʻana i nā pale e laka ma luna o lākou. Ua like nā pūnaewele T me nā koa, e luku ana i kanā mea hoʻouka kaua i ʻike ʻia e ka ʻōnaehana ʻike.
ʻO ka ʻenehana cell T Chimeric antigen receptor (CAR): he ʻano cellular hānaiimmunotherapy (ACI). Hōʻike ka cell T o ka mea maʻi iā CAR ma o ke kūkulu hou ʻana i nā ʻano geneticʻenehana, ka mea e hoʻolilo ai i nā pūnaewele effector T i ʻoi aku ka kikoʻī, make a mau loa ma mua onā pūnaewele pale maʻamau, a hiki ke lanakila ma luna o ka microenvironment immunosuppressive kūloko opuʻupuʻu a uhaki i ka hoʻomanawanui o ka pale ʻana o ka mea hoʻokipa. He lāʻau lapaʻau kūikawā kēia no ka pale ʻana i ka puʻupuʻu.
ʻO ke kumumanaʻo o CART, ʻo ia ka lawe ʻana i ka "mana maʻamau" o nā pūnaewele T 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 nuimea kaua antipersonnel "chimeric antigen receptor (CAR)", a laila hoʻokomo i nā cell T i hoʻololi ʻiahoʻi i loko o ke kino o ka mea maʻi, e like nā mea loaʻa kelepona hou i hoʻololi ʻia me ke kau ʻana i kahi ʻōnaehana radar,ka mea e hiki ai 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 ʻehānā hanauna. Hoʻohana mākou i ka hanauna hou loa ʻo CART.
1sthanauna: Hoʻokahi wale nō ʻāpana hōʻailona intracellular a me ka pale ʻana o ka tumorʻaʻole maikaʻi ka hopena.
2ndhanauna: Hoʻohui ʻia kahi molekala hoʻouluulu like ma ke kumu o ka hanauna mua, a me kaua hoʻomaikaʻi ʻia ka hiki o nā pūnaewele T ke pepehi i nā ʻōpū.
3rdhanauna: Ma muli o ka lua o ka hanauna o CAR, ka hiki o nā pūnaewele T ke kāohi i ka tumorua hoʻomaikaʻi nui ʻia ka ulu ʻana a me ka hoʻolaha ʻana i ka apoptosis.
4thhanauna: Hiki i nā pūnaewele CAR-T ke komo i ka hoʻomaʻemaʻe ʻana o ka heluna o nā pūnaewele tumor eke hoʻoulu nei i ka mea hoʻololi transcription NFAT ma hope e hoʻoulu i ka interleukin-12 ma hope o CARʻike i ka antigen i manaʻo ʻia.
| Hanauna | Hoʻoulu ʻana Kumu | Hiʻona |
| 1st | CD3ζ | Hoʻāla kūikawā ʻia ka pūnaewele T, he pūnaewele cytotoxic T, akā ʻaʻole hiki ke hoʻonui a ola i loko o ke kino. |
| 2nd | CD3ζ+CD28/4-1BB/OX40 | Hoʻohui i ka costimulator, hoʻomaikaʻi i ka ʻawahia o ke kelepona, hiki ke hoʻonui ʻia me ka palena palena. |
| 3rd | CD3ζ+CD28/4-1BB/OX40+CD134 /CD137 | E hoʻohui i 2 mau mea hoʻouluulu, hoʻomaikaʻika hiki ke hoʻonui a me ka ʻawahia. |
| 4th | ʻO ke kine pepehi kanaka/Amored CAR-T (12IL) E hele iā CAR-T | Hoʻohui i ka gene pepehi kanaka, hōʻike i ka mea pale kino a me nā hana kaohi pololei ʻē aʻe. |
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) Hoʻāla ʻia nā pūnaewele T: nā momi magnetic (nā pūnaewele dendritic hana) i uhi ʻia me nā antibodieshoʻohana ʻia e hoʻoulu i nā pūnaewele T.
3) Transfection: Ua hana ʻia nā pūnaewele T ma ke ʻano genetic e hōʻike i ka CAR in vitro.
4) Hoʻonui: Hoʻonui ʻia nā pūnaewele T i hoʻololi ʻia i ka genetics in vitro.
5) Chemotherapy: Hoʻomaʻamaʻa mua ʻia ka mea maʻi me ka chemotherapy ma mua o ka hoʻokomo hou ʻana o nā cell T.
6) Hoʻokomo hou ʻia: Hoʻokomo hou nā pūnaewele T i hoʻololi ʻia i ka genetics i loko o ka mea maʻi.
Nā hōʻailona
Nā hōʻailona no CAR-T
ʻŌnaehana hanu: Ka maʻi ʻaʻai māmā (Small cell carcinoma, squamous cell carcinoma,adenocarcinoma), ke kanesa nasopharynx, a pēlā aku.
ʻŌnaehana hoʻoheheʻe: ʻO ke kanesa o ke akepaʻa, ka ʻōpū a me ka colorectal, a pēlā aku.
ʻŌnaehana mimi: ʻO ka maʻi kanesa puʻupaʻa a me ka adrenal a me ka maʻi kanesa metastatic, a pēlā aku.
ʻŌnaehana koko: Leukemia lymphoblastic koʻikoʻi a me ka maʻi mau (T lymphomai kāpae ʻia) etc.
ʻO ke kanesa ʻē aʻe: Malignant melanoma, umauma, prostate a me ke kanesa alelo, etc.
ʻO ke ʻoki kino e wehe ai i ka ʻeha mua, akā haʻahaʻa ka palekana, a lohi ka hoʻōla hou ʻana.
Nā puʻupuʻu me ka metastasis ākea i hiki ʻole ke hoʻomau i ke ʻoki ʻana.
Nui a ʻaʻole paha i pili ka hopena ʻaoʻao o ka chemotherapy a me ka radiotherapy i ka chemotherapy a me ka radiotherapy.
Pale i ka hoʻi hou ʻana o ka maʻi puʻupuʻu ma hope o ke ʻoki ʻana, chemotherapy a me radiotherapy.
Nā Pōmaikaʻi
1) Hoʻopaʻa nui ʻia nā pūnaewele CAR T a hiki ke pepehi i nā pūnaewele tumor me ka antigen specificity 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.