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 pale i kahi pūnaewele o nā sela, nā ʻiʻo, a me nā ʻāpana e hana pū ana e pale i ke kino.ʻO kekahi o nā pūnaewele koʻikoʻi e pili ana he mau keʻokeʻo keʻokeʻo, i kapa ʻia hoʻi nā leukocytes, i hele mai i ʻelua mau ʻano kumu e hui pū ai e ʻimi a luku i nā mea ola a i ʻole nā mea.
ʻO nā ʻano leukocytes ʻelua:
Ø phagocytes, nā pūnaewele e nahu i nā mea ola kino
Ø nā lymphocytes, nā pūnaewele e hiki ai i ke kino ke hoʻomanaʻo a ʻike i nā mea hoʻouka kaua mua a kōkua i ke kino e luku iā lākou
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 e pili ana i ka maʻi bacteria, hiki iā lākou ke kauoha i ka hoʻāʻo koko e ʻike inā he nui ka nui o nā neutrophils i hoʻokumu ʻia e ka maʻi.ʻO nā ʻano phagocytes ʻē aʻe i kā lākou mau hana ponoʻī e hōʻoia i ka pane kūpono o ke kino i kahi ʻano mea hoʻouka kaua.
ʻO nā ʻano lymphocytes ʻelua he B lymphocytes a me T lymphocytes.Hoʻomaka ka lymphocytes i loko o ka iwi iwi a noho ma laila a oʻo i loko o nā pūnaʻi B, a i ʻole lākou e haʻalele i ka thymus gland, kahi e oʻo ai lākou i loko o nā sela T.He mau hana kaawale ko B lymphocytes a me T lymphocytes: He like ko B lymphocytes me ka ʻōnaehana naʻauao koa o ke kino, e ʻimi ana i kā lākou mau pahu hopu a hoʻouna i nā pale e laka iā lākou.ʻO nā pūnaewele T e like me nā koa, e luku ana i nā mea hoʻouka kaua i ʻike ʻia e ka ʻōnaehana naʻauao.
Hoʻokumu ʻia ka ʻōnaehana pale i kahi pūnaewele o nā sela, nā ʻiʻo, a me nā ʻāpana e hana pū ana e pale i ke kino.ʻO kekahi o nā pūnaewele koʻikoʻi e pili ana he mau keʻokeʻo keʻokeʻo, i kapa ʻia hoʻi nā leukocytes, i hele mai i ʻelua mau ʻano kumu e hui pū ai e ʻimi a luku i nā mea ola a i ʻole nā mea.
ʻO nā ʻano leukocytes ʻelua:
Ø phagocytes, nā pūnaewele e nahu i nā mea ola kino
Ø nā lymphocytes, nā pūnaewele e hiki ai i ke kino ke hoʻomanaʻo a ʻike i nā mea hoʻouka kaua mua a kōkua i ke kino e luku iā lākou
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 e pili ana i ka maʻi bacteria, hiki iā lākou ke kauoha i ka hoʻāʻo koko e ʻike inā he nui ka nui o nā neutrophils i hoʻokumu ʻia e ka maʻi.ʻO nā ʻano phagocytes ʻē aʻe i kā lākou mau hana ponoʻī e hōʻoia i ka pane kūpono o ke kino i kahi ʻano mea hoʻouka kaua.
ʻO nā ʻano lymphocytes ʻelua he B lymphocytes a me T lymphocytes.Hoʻomaka ka lymphocytes i loko o ka iwi iwi a noho ma laila a oʻo i loko o nā pūnaʻi B, a i ʻole lākou e haʻalele i ka thymus gland, kahi e oʻo ai lākou i loko o nā sela T.He mau hana kaawale ko B lymphocytes a me T lymphocytes: He like ko B lymphocytes me ka ʻōnaehana naʻauao koa o ke kino, e ʻimi ana i kā lākou mau pahu hopu a hoʻouna i nā pale e laka iā lākou.ʻO nā pūnaewele T e like me nā koa, e luku ana i nā mea hoʻouka kaua i ʻike ʻia e ka ʻōnaehana naʻauao.
ʻO Chimeric antigen receptor (CAR) T cell technology: he ʻano o ka immunotherapy cellular adoptive (ACI).Hōʻike ka pūnaʻi T o ka maʻi i ka CAR ma o ka ʻenehana hoʻoponopono hou ʻana, ka mea e ʻoi aku ka manaʻo o nā pūnaew T effector, make a hoʻomau ʻia ma mua o nā cell immune maʻamau, a hiki ke lanakila i ka microenvironment immunosuppressive kūloko o ka maʻi maʻi a wāwahi i ka hoʻomanawanui ʻole.ʻO kēia kahi lāʻau lapaʻau anti-tumor maʻamau.
ʻO ke kumu o CART ka lawe ʻana i ka "ʻano maʻamau" o nā pūnaewele T immune o ka mea maʻi a hoʻomau i ka ʻenekinia gene, e hōʻuluʻulu i loko o ka vitro no nā pahu kikoʻī kikoʻī o nā mea kaua antipersonnel nui "chimeric antigen receptor (CAR)", a laila hoʻokomo i ka mea hoʻololi. Hoʻi hou nā pūnaewele T i loko o ke kino o ka mea maʻi, e like ana nā mea hoʻopaʻa kelepona hou i hoʻololi ʻia e hoʻokomo i kahi ʻōnaehana radar, hiki ke alakaʻi i nā pūnae T e ʻimi a luku i nā maʻi maʻi.
ʻO ka pono o CART ma BPIH
Ma muli o nā ʻokoʻa o ke ʻano o ka domain signal intracellular, ua hoʻomohala ʻo CAR i ʻehā mau hanauna.Hoʻohana mākou i ka hanauna hou loa CART.
1Sthanauna: Hoʻokahi wale nō ʻāpana hōʻailona intracellular a ʻaʻole maikaʻi ka hopena hoʻopaʻa ʻana i ka tumo.
2ndhanauna: Hoʻohui ʻia kahi mole hoʻoulu ʻia ma ke kumu o ka hanauna mua, a ua hoʻomaikaʻi ʻia ka hiki o nā cell T ke pepehi i nā ʻōpū.
3rdhanauna: Ma muli o ka lua o ka hanauna o CAR, ua hoʻomaikaʻi maikaʻi ʻia ka hiki o nā pūnae T e keʻakeʻa i ka ulu ʻana o ka maʻi maʻi a hoʻoikaika i ka apoptosis.
4thhanauna: Hiki ke komo i nā pūnaewele CAR-T i ka hoʻomaʻemaʻe ʻana i ka heluna o nā cell tumo ma o ka hoʻāla ʻana i ka helu transcription downstream NFAT e hoʻoulu i ka interleukin-12 ma hope o ka ʻike ʻana o CAR i ka antigen target.
Kaʻina hana lapaʻau
1) Hoʻokaʻawale ʻia ke koko keʻokeʻo: Ua hoʻokaʻawale ʻia nā keʻena T o ka maʻi mai ke koko ʻaoʻao;
2) Hoʻoulu ʻia nā pūnaewele T: hoʻohana ʻia nā peʻa magnetic (nā pūnaewele dendritic artificial) i uhi ʻia me nā antibodies no ka hoʻōla ʻana i nā cell T;
Ka hoʻololi: Ua hoʻomohala ʻia nā pūnaewele T e hōʻike i ka CAR in vitro.
3) Hoʻonui ʻia: Hoʻonui ʻia nā cell T i hoʻololi ʻia i loko o ka vitro.
4) Chemotherapy: Hoʻomaʻamaʻa mua ʻia ka mea maʻi me ka chemotherapy ma mua o ka reinfusion cell T;
5) Re-infusion: Hoʻihoʻi hou ʻia nā cell T i hoʻololi ʻia i loko o ka mea maʻi.
Pono:
1)ʻO nā pūnaewele CAR T ka mea i manaʻo nui ʻia a hiki ke pepehi i nā cell tumor me ka kikoʻī antigen i ʻoi aku ka maikaʻi.
2)ʻO ka lāʻau lapaʻau CAR-T he liʻiliʻi 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 hoʻomaopopo wale i nā antigens peptide, akā ʻo 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 immune 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.