He aha te CAR-T (Chimeric Antigen Receptor T-cell)?
Tuatahi, me titiro tātou ki te pūnaha ārai mate o te tangata.
Ko te pūnaha ārai mate he whatunga o ngā pūtau, ngā kiko, me ngā whekau e mahi tahi ana ki tetiaki i te tinana. Ko tētahi o ngā pūtau nui e whai wāhi ana ko ngā pūtau toto mā, e kiia ana hoki ko ngā leukocyte,e rua ngā momo matua e hono ana ki te rapu me te whakangaro i ngā rauropi e puta ai te mate,ngā matū
Ko ngā momo matua e rua o ngā leukocyte ko:
Ngā pūtau whakapūpū, arā, ngā pūtau e ngaungau ana i ngā rauropi whakaeke.
Ngā pūtau lymphocytes, arā, ngā pūtau e āhei ai te tinana ki te maumahara me te kite i ngā whakaeke o mua, ā, e āwhina ana hokika whakangaromia rātou e te tinana.
He maha ngā pūtau rerekē e kiia ana he pūtau whakapūpū. Ko te momo tino noa ko te neutrophil,e whawhai ana i ngā huakita. Mena kei te āwangawanga ngā tākuta mō te mate huakita, ka tono pea rātouhe whakamātautau toto hei tirotiro mēnā kua piki ake te maha o ngā neutrophils i roto i te tūroro i puta mai i te mate.
He mahi anō tā ētahi atu momo pūtau whakapūngao hei whakarite kia tika te urupare a te tinana.ki tētahi momo kaipahua motuhake.
Ko ngā momo lymphocytes e rua ko ngā lymphocytes B me ngā lymphocytes T. Ka tīmata ngā lymphocytesi roto i te hinu wheua, ā, ka noho ki reira ka pakari hei pūtau-B, ka wehe atu rānei ki te thymusrepe, te wāhi e pakeke ai hei pūtau-T. He rerekē ngā pūtau toto-B me ngā pūtau toto-Tngā mahi: He rite ngā pūtau toto B ki te pūnaha matauranga hōia o te tinana, e rapu ana i ā rātoungā ūnga me te tuku parepare hei raka ki a rātou. He rite ngā pūtau-T ki ngā hōia, e whakangaro ana i tengā kaipahua kua tautuhia e te pūnaha mōhiohio.
Hangarau pūtau-T Chimeric antigen receptor (CAR): he momo pūtau whāngaite rongoā ārai mate (ACI). Ka whakaatuhia e te pūtau-T o te tūroro te CAR mā te hanga anō irahangarau, e hanga ana i ngā pūtau-T whaihua kia whaia ake, kia whakamatea, kia mau tonu hoki ingā pūtau ārai mate tuku iho, ā, ka taea te wikitoria i te taiao ārai mate ā-rohe ote pukupuku me te wawahi i te manawanui o te pūnaha ārai mate o te tangata. He rongoā motuhake tēnei mō ngā pūtau ārai mate pukupuku.
Ko te kaupapa matua o te CART he tango i te "putanga noa" o ngā pūtau-T ārai mate o te tūroro.me te haere tonu i te hangarau ira, te kohikohi i roto i te vitro mō ngā whāinga motuhake o te pukupuku o te nuite patu ārai-tangata "chimeric antigen receptor (CAR)", kātahi ka werohia ngā pūtau-T kua whakarerekētiaki roto i te tinana o te tūroro, ka rite ngā kaiwhakawhiwhi pūtau hou kua whakarerekētia ki te tāuta i tētahi pūnaha radar,e āhei ana ki te ārahi i ngā pūtau-T ki te kimi me te whakangaro i ngā pūtau matepukupuku.
Te painga o te CART i BPIH
Nā ngā rerekētanga o te hanganga o te rohe tohu ā-roto, kua whakawhanakehia e CAR ētahi atu e whāngā whakatipuranga. E whakamahi ana mātou i te CART o te whakatipuranga hou.
1stwhakatupuranga: Kotahi anake te wāhanga tohu ā-roto me te aukati i te pukupukukāore i pai te pānga.
2ndwhakatupuranga: I tāpirihia he ngota whakaoho-tahi i runga i te kaupapa o te whakatupuranga tuatahi, me tekua pai ake te kaha o ngā pūtau-T ki te patu i ngā pukupuku.
3rdwhakatupuranga: I runga i te whakatupuranga tuarua o CAR, ko te kaha o ngā pūtau-T ki te aukati i te pukupukui tino pai ake te tipu me te whakatairanga i te apoptosis.
4thwhakatupuranga: Ka taea e ngā pūtau CAR-T te whai wāhi ki te whakakore i te taupori pūtau pukupuku mā tete whakahohe i te take whakawhiti o raro o te NFAT hei whakaoho i te interleukin-12 i muri i te CARka mōhio ki te antigen ūnga.
| Whakatupuranga | Whakaohooho Tauwehenga | Āhuatanga |
| 1st | CD3ζ | He whakahohenga motuhake o ngā pūtau-T, he pūtau-T paitini, engari kāore e taea te tipu me te ora i roto i te tinana. |
| 2nd | CD3ζ+CD28/4-1BB/OX40 | Tāpirihia he whakaohooho, whakapai ake i te paitini pūtau, he iti te kaha ki te whakatipu. |
| 3rd | CD3ζ+CD28/4-1BB/OX40+CD134 /CD137 | Tāpirihia kia rua ngā mea whakaohooho, whakapai akete kaha ki te tipu me te paitini. |
| 4th | Ira whakamomori/Amored CAR-T (12IL) Haere CAR-T | Whakauruhia te ira whakamomori, te whakaatu i te āhuatanga ārai mate me ētahi atu tikanga whakahaere tika. |
Te tikanga maimoatanga
1) Te wehe i ngā pūtau toto mā: Ka wehea ngā pūtau-T o te tūroro mai i te toto ā-taha.
2) Te whakahohenga o ngā pūtau-T: ko ngā pirepire aukume (ngā pūtau dendritic horihori) kua pania ki ngā paturopi kae whakamahia ana hei whakahohe i ngā pūtau-T.
3) Whakawhitinga ira: Ka hangaia ngā pūtau-T kia whakaatu i te CAR i roto i te vitro.
4) Whakarei ake: Ka whakarei ake ngā pūtau-T kua whakarerekētia te ira i roto i te vitro.
5) Te rongoā matū: Ka rongoātia te tūroro ki te rongoā matū i mua i te whakaurunga anō o ngā pūtau-T.
6) Te werohanga anō: Ka werohanga anō ngā pūtau-T kua whakarerekētia te ira ki roto i te tūroro.
Ngā tohu
Ngā tohu mō te CAR-T
Pūnaha manawa: Matepukupuku pūkahukahu (matepukupuku pūtau iti, matepukupuku pūtau pūrua,adenocarcinoma), mate pukupuku ihu, me ētahi atu
Pūnaha nakunaku: Te mate pukupuku o te ate, te puku me te koroni, me ētahi atu.
Pūnaha mimi: Te mate pukupuku o te whatukuhu me te adrenal me te mate pukupuku metastatic, me ētahi atu.
Pūnaha toto: Leukemia lymphoblastic whakapeka me te mau tonu (T lymphoma)kāore i whakaurua) me ētahi atu
Ētahi atu mate pukupuku: Te mate pukupuku melanoma kino, te mate pukupuku o te ū, te prostate me te arero, me ētahi atu.
I whakahaerehia he pokanga hei tango i te whara tuatahi, engari he iti te kaha ārai mate, ā, he puhoi te whakaora.
He pukupuku kua horapa te horapa, kāore e taea te mahi pokanga.
He nui, he kore rānei e pāngia e ngā pānga taha o te chemotherapy me te radiotherapy e te chemotherapy me te radiotherapy.
Ārai i te hokinga mai o te pukupuku i muri i te pokanga, te chemotherapy me te radiotherapy.
Ngā Painga
1) He tino arotahi ngā pūtau CAR T, ā, ka taea e rātou te patu i ngā pūtau pukupuku me te motuhake ki te antigen.
2) He iti ake te wā e hiahiatia ana mō te rongoā pūtau CAR-T. Ko te wā poto rawa atu e hiahiatia ana e CAR T hei whakatipu i ngā pūtau T nā te mea he iti ake ngā pūtau e hiahiatia ana i raro i te pānga maimoatanga kotahi. Ka taea te whakapoto i te huringa whakatipu vitro ki te 2 wiki, ā, ka tino whakaitihia te wā tatari.
3) Ka taea e CAR te kite ehara i te mea ko ngā peptide antigens anake, engari ko ngā huka me ngā lipid antigens hoki, ka whakawhānui ake i te whānuitanga o ngā mate pukupuku. Kāore hoki te rongoā CAR T e herea ana e ngā pūmua antigens o ngā pūtau pukupuku. Ka taea e CAR T te whakamahi i ngā huka me ngā lipid antigens kore-pūmua o ngā pūtau pukupuku hei tautuhi i ngā antigens i roto i ngā whānuitanga maha.
4) He whānui te āheinga o te CAR-T ki te whakaputa anō. Nā te mea kei roto i ngā pūtau pukupuku maha ētahi wāhi, pērā i te EGFR, ka taea te whakamahi whānui i tētahi ira CAR mō tēnei antigen ina oti te hanga.
5) He mahi maumahara ā-pūtau CAR T ā, ka taea e rātou te ora i roto i te tinana mō te wā roa. He mea nui ki te taha haumanu hei ārai i te hokinga mai o te pukupuku.