He aha ka CAR-T (Chimeric Antigen Receptor T-cell)?
ʻO ka mea mua, e nānā kākou i ke kino o ke kanaka.
Hoʻokumu ʻia ka ʻōnaehana immune me kahi pūnaewele o nā sela, nā ʻiʻo, a me nā ʻāpana e hana pū anapale i ke kino.ʻO kekahi o nā mea koʻikoʻi e pili ana i ke koko keʻokeʻo, i kapa ʻia hoʻi nā leukocytes,i hele mai i loko o ʻelua mau ʻano kumu i hui pū ʻia e ʻimi a luku i nā mea ola kino a i ʻolemea waiwai.
ʻO nā ʻano leukocytes ʻelua:
Phagocytes, nā pūnaewele e nahu i nā mea ola kino.
Lymphocytes, nā pūnaewele e hiki ai i ke kino ke hoʻomanaʻo a hoʻomaopopo i nā mea hoʻouka mua a kōkuae hoopau ke kino ia lakou.
Ua manaʻo ʻia kekahi mau ʻāpana like ʻole he phagocytes.ʻO ka ʻano maʻamau ka neutrophil,ka mea e hakakā mua i ka bacteria.Inā hopohopo nā kauka i kahi maʻi bacteria, hiki iā lākou ke kauohahe ho'āʻo koko e ʻike inā loaʻa i ka mea maʻi ka nui o nā neutrophils i hoʻāla ʻia e ka maʻi.
Aia nā ʻano phagocytes ʻē aʻe i kā lākou hana ponoʻī e hōʻoia i ka pane kūpono o ke kinoi kekahi ʻano mea hoʻouka kaua.
ʻO nā ʻano lymphocytes ʻelua he B lymphocytes a me T lymphocytes.Hoʻomaka ka lymphocytesi loko o ka iwi iwi a noho paha i laila a oʻo i loko o nā pūnaʻi B, a i ʻole lākou e haʻalele no ka thymusgland, kahi e oʻo ai i loko o nā pūnaewele T.He kaʻawale nā lymphocytes B a me T lymphocytesnā hana: B like nā lymphocytes me ka ʻōnaehana naʻauao koa o ke kino, e ʻimi ana i kā lākounā pahu hopu a me ka hoʻouna ʻana i nā pale e laka iā lākou.Ua like nā pūnae T me nā koa, e luku ana i kanā mea hoʻouka kaua i ʻike ʻia e ka ʻōnaehana naʻauao.
ʻO Chimeric antigen receptor (CAR) ʻenehana T cell: he ʻano o ka cellular adoptiveimmunotherapy (ACI).Hōʻike ke kelepona T o ka maʻi i ka CAR ma o ka hana hou ʻanaʻenehana, ka mea e hoʻomake ai i nā pūnaewele T effector, make a hoʻomaumaʻamau nā mea hoʻomaʻemaʻe kino, a hiki ke lanakila kūloko immunosuppressive microenvironment oʻo ka ʻōpū a me ka uhaki ʻana i ka hoʻomanawanui ʻole.ʻO kēia kahi lāʻau lapaʻau kūʻokoʻa anti-tumo.
ʻO ke kumu o ka CART ka lawe ʻana i ka "mana maʻamau" o nā pūnaewele T immune ponoʻī o ka mea maʻia hoʻomau i ka ʻenekinia gene, hōʻuluʻulu in vitro no nā pahuhopu kikoʻī o ka nuimea kaua antipersonnel "chimeric antigen receptor (CAR)", a laila hoʻokomo i nā pūnae T i hoʻololi ʻiae hoʻi hou i loko o ke kino o ka mea maʻi, e like me nā mea hoʻokipa kelepona hou e hoʻokomo i kahi ʻōnaehana radar,hiki iā ia ke alakaʻi i nā pūnaewele T e ʻimi a luku i nā maʻi maʻi maʻi.
ʻO ka pono o CART ma BPIH
Ma muli o ka ʻokoʻa o ke ʻano o ka domain signal intracellular, ua hoʻomohala ʻo CAR i ʻehānā hanauna.Hoʻohana mākou i ka hanauna hou loa CART.
1sthanauna: Hoʻokahi wale nō ʻāpana hōʻailona intracellular a me ka hoʻopaʻa ʻana i ka tumorʻilihune ka hopena.
2ndhanauna: Hoʻohui i kahi mole hoʻoulu ʻia ma ke kumu o ka hanauna mua, a me kaUa hoʻomaikaʻi ʻia ka hiki o nā pūnae T e pepehi i nā ʻōpū.
3rdhanauna: Ma muli o ka lua o ka hanauna o CAR, hiki i nā pūnae T ke keʻakeʻa i ka maʻi maʻiUa hoʻomaikaʻi maikaʻi ʻia ka proliferation a me ka paipai ʻana i ka apoptosis.
4thhanauna: Hiki i nā pūnaewele CAR-T ke komo i ka hoʻomaʻemaʻe ʻana i ka heluna o nā pūnana maʻi maʻi ee ho'āla ana i ka helu transcription downstream NFAT e hoʻoulu i ka interleukin-12 ma hope o CARʻike i ka antigen target.
| He hanauna | Hoʻoulu ʻana Kumu | Hiʻona |
| 1st | CD3ζ | ʻO ka hoʻoulu ʻana o ka cell T, cytotoxic T cell, 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 ʻona o ka cell, ka hiki ke hoʻonui. |
| 3rd | CD3ζ+CD28/4-1BB/OX40+CD134 /CD137 | Hoʻohui i 2 costimulators, hoʻomaikaʻihiki ke hoʻonui a me ka ʻawaʻawa. |
| 4th | Gene pepehi kanaka/Amored CAR-T (12IL) Hele CAR-T | E hoʻohui i ke ʻano pepehi kanaka, e hōʻike i ka mea palekana a me nā ana hoʻomalu pololei ʻē aʻe. |
Kaʻina hana lapaʻau
1) Hoʻokaʻawale ʻia ke koko keʻokeʻo: Hoʻokaʻawale ʻia nā sela T o ka maʻi mai ke koko ʻaoʻao.
2) Hoʻoulu ʻia nā pūnaewele T: nā peʻa magnetic (nā pūnaewele dendritic artificial) i uhi ʻia me nā antibodies.hoʻohana ʻia no ka hoʻāla ʻana i nā cell T.
3) Ka hoʻololi ʻana: Ua hoʻomohala ʻia nā pūnaewele T e hōʻike i ka CAR in vitro.
4) Hoʻonui ʻia: Hoʻonui ʻia nā cell T i hoʻololi ʻia i loko o ka vitro.
5) Chemotherapy: Hoʻomaʻamaʻa mua ʻia ka mea maʻi me ka chemotherapy ma mua o ka reinfusion cell T.
6) Re-infusion: Hoʻokomo hou ʻia nā cell T i hoʻololi ʻia i loko o ka mea maʻi.
Nā hōʻailona
Nā hōʻailona no CAR-T
Pūnaehana hanu: Ka ma'i 'a'ai (Small cell carcinoma, squamous cell carcinoma,adenocarcinoma), nasopharynx cancer, etc.
Pūnaehana digestive: ate, ʻōpū a me ka colorectal cancer, etc.
Pūnaehana urinary: ʻO ka maʻi maʻi a me ka maʻi maʻi adrenal a me ka cnacer metastatic, etc.
Pūnaehana koko: Leukemia lymphoblastic maʻi a maʻi (T lymphomawehe ʻia) etc.
ʻO nā maʻi maʻi ʻē aʻe: Ka maʻi maʻi ʻino, ka umauma, ka prostate a me ke alelo, a pēlā aku.
ʻO ka ʻoki ʻana no ka wehe ʻana i ka ʻeha mua, akā haʻahaʻa ka pale ʻana, a lohi ka recoery.
ʻO nā puʻupuʻu me ka metastasis ākea ʻaʻole hiki ke hoʻomaka i ke kaʻa.
ʻO ka hopena ʻaoʻao o ka chemotherapy a me ka radiotherapy he nui a ʻaʻole ʻike i ka chemotherapy a me ka radiotherapy.
Kāohi i ka hoʻi hou ʻana o ka maʻi maʻi ma hope o ka ʻoki ʻana, ka chemotherapy a me ka radiotherapy.
Pono
1) ʻO nā pūnaewele CAR T ka mea i manaʻo nui ʻia a hiki ke pepehi i nā pūnana maʻi me ka kikoʻī antigen i ʻoi aku ka maikaʻi.
2) ʻO ka hoʻomaʻamaʻa cell CAR-T pono ka liʻiliʻi o ka manawa.Pono ʻo CAR T i ka manawa pōkole loa e hoʻomaʻamaʻa i nā cell T no ka mea he liʻiliʻi nā cell ma lalo o ka hopena lapaʻau like.Hiki ke hoʻopōkole ʻia ka pōʻai moʻomeheu vitro i 2 mau pule, ka mea i hōʻemi nui i ka manawa kali.
3) ʻAʻole hiki i ka CAR ke ʻike i nā antigens peptide wale nō, akā i ke kō a me nā antigens lipid, e hoʻonui ana i ka pae o nā antigens tumor.ʻAʻole i kaupalena ʻia ka lāʻau lapaʻau CAR T e nā antigens protein o nā cell tumor.Hiki i ka CAR T ke hoʻohana i ke kō a me ka lipid non-protein antigens o nā pūnaewele tumo e ʻike ai i nā antigens ma nā ʻano he nui.
4) Loaʻa i ka CAR-T kahi ākea - spectrum reproducibility.Ma muli o ka hōʻike ʻia ʻana o kekahi mau pūnaewele i loko o nā pūnaewele tumo 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 kūlohelohe a hiki ke ola i loko o ke kino no ka manawa lōʻihi.He koʻikoʻi koʻikoʻi ia e pale ai i ka hoʻi hou ʻana o ka maʻi maʻi.