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 hei tiaki i te tinana. Ko tētahi o ngā pūtau nui e whai wāhi ana ko ngā pūtau toto mā, e kiia ana ko ngā leukocyte, e rua ngā momo matua e hono ana ki te rapu me te whakangaro i ngā rauropi, i ngā matū rānei e puta ai te mate.
Ko ngā momo matua e rua o ngā leukocyte ko:
Ø ngā pūtau whakapūpū, arā, ngā pūtau e ngaungau ana i ngā rauropi whakaeke
Ngā pūtau lymphocytes Ø, arā, ngā pūtau e āhei ai te tinana ki te maumahara me te kite i ngā whakaeke o mua, ā, e āwhina ana hoki i te tinana ki te whakangaro i a rātou.
He maha ngā pūtau rerekē e kiia ana he pūtau whakapūpū. Ko te momo tino noa ko te neutrophil, e whawhai ana ki ngā huakita. Mena kei te āwangawanga ngā tākuta mō te mate huakita, ka tono pea rātou i tētahi whakamātautau toto hei tirotiro mena kua piki ake te maha o ngā neutrophil i puta mai i te mate. He mahi anō tā ētahi atu momo pūtau whakapūpū hei whakarite kia tika te urupare a te tinana ki tētahi momo whakaeke motuhake.
Ko ngā momo lymphocytes e rua ko ngā lymphocytes B me ngā lymphocytes T. Ka tīmata ngā lymphocytes i roto i te hinu wheua, ka noho ki reira ka pakeke hei pūtau B, ka wehe atu rānei ki te repe thymus, ka pakeke hei pūtau T. He rerekē ngā mahi a ngā lymphocytes B me ngā lymphocytes T: He rite ngā lymphocytes B ki te pūnaha matauranga hōia o te tinana, e rapu ana i ā rātou ūnga me te tuku parepare hei raka ki a rātou. He rite ngā pūtau T ki ngā hōia, e whakangaro ana i ngā kaiwhakaeke kua tautuhia e te pūnaha matauranga.
Ko te pūnaha ārai mate he whatunga o ngā pūtau, ngā kiko, me ngā whekau e mahi tahi ana hei tiaki i te tinana. Ko tētahi o ngā pūtau nui e whai wāhi ana ko ngā pūtau toto mā, e kiia ana ko ngā leukocyte, e rua ngā momo matua e hono ana ki te rapu me te whakangaro i ngā rauropi, i ngā matū rānei e puta ai te mate.
Ko ngā momo matua e rua o ngā leukocyte ko:
Ø ngā pūtau whakapūpū, arā, ngā pūtau e ngaungau ana i ngā rauropi whakaeke
Ngā pūtau lymphocytes Ø, arā, ngā pūtau e āhei ai te tinana ki te maumahara me te kite i ngā whakaeke o mua, ā, e āwhina ana hoki i te tinana ki te whakangaro i a rātou.
He maha ngā pūtau rerekē e kiia ana he pūtau whakapūpū. Ko te momo tino noa ko te neutrophil, e whawhai ana ki ngā huakita. Mena kei te āwangawanga ngā tākuta mō te mate huakita, ka tono pea rātou i tētahi whakamātautau toto hei tirotiro mena kua piki ake te maha o ngā neutrophil i puta mai i te mate. He mahi anō tā ētahi atu momo pūtau whakapūpū hei whakarite kia tika te urupare a te tinana ki tētahi momo whakaeke motuhake.
Ko ngā momo lymphocytes e rua ko ngā lymphocytes B me ngā lymphocytes T. Ka tīmata ngā lymphocytes i roto i te hinu wheua, ka noho ki reira ka pakeke hei pūtau B, ka wehe atu rānei ki te repe thymus, ka pakeke hei pūtau T. He rerekē ngā mahi a ngā lymphocytes B me ngā lymphocytes T: He rite ngā lymphocytes B ki te pūnaha matauranga hōia o te tinana, e rapu ana i ā rātou ūnga me te tuku parepare hei raka ki a rātou. He rite ngā pūtau T ki ngā hōia, e whakangaro ana i ngā kaiwhakaeke kua tautuhia e te pūnaha matauranga.
Hangarau pūtau-T Chimeric antigen receptor (CAR): he momo rongoā ārai mate pūtau whāngai (ACI). Ka whakaatuhia e te pūtau-T o te tūroro te CAR mā te hangarau hanga ira, ka nui ake te aro, te whakamate me te pumau o ngā pūtau-T whai pānga i ngā pūtau ārai mate tuku iho, ā, ka taea te wikitoria i te taiao iti ārai mate ā-rohe o te pukupuku me te wawahi i te manawanui o te ārai mate o te tinana. He rongoā ārai mate pūtau motuhake tēnei.
Ko te mātāpono o te CART he tango i te "putanga noa" o ngā pūtau-T ārai mate o te tūroro, ka haere tonu ki te hanga ira, ka huihui i roto i te vitro mō ngā ūnga motuhake ki te pukupuku o te "kaiwhakawhiwhi antigen chimeric (CAR)" o te patu ā-iwi nui, kātahi ka whakaurua ngā pūtau-T kua whakarerekētia ki roto i te tinana o te tūroro. Ko ngā kaiwhakawhiwhi pūtau hou kua whakarerekētia ka rite ki te tāuta i tētahi pūnaha radar, ka taea 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, e whā ngā whakatipuranga kua whakawhanakehia e CAR. E whakamahia ana e mātou te whakatipuranga hou o CART.
1stwhakatupuranga: Kotahi anake te wāhanga tohu ā-roto, ā, he ngoikore te pānga aukati pukupuku.
2ndwhakatupuranga: I tāpirihia he ngota whakaoho-ā-tahi i runga i te kaupapa o te whakatupuranga tuatahi, ā, i whakapaitia te kaha o ngā pūtau-T ki te patu i ngā pukupuku.
3rdwhakatupuranga: I runga i te whakatupuranga tuarua o CAR, i tino pai ake te kaha o ngā pūtau-T ki te aukati i te tipu o te pukupuku 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 te whakahohe i te take whakawhiti NFAT ki te whakaoho i te interleukin-12 i muri i te mohiotanga o te CAR ki te antigen ūnga.
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: ka whakamahia ngā pirepire aukume (ngā pūtau dendritic horihori) kua pania ki ngā paturopi hei whakahohe i ngā pūtau-T;
Whakawhitinga ira: Ka hangaia ngā pūtau-T hei whakaatu i te CAR i roto i te vitro.
3) Whakarei ake: Ka whakarei ake ngā pūtau-T kua whakarerekētia te ira i roto i te vitro.
4) Te rongoā matū: Ka rongoātia te tūroro ki te rongoā matū i mua i te whakaurunga anō o te pūtau-T;
5) Te werohanga anō: Ka werohanga anō ngā pūtau-T kua whakarerekētia te ira ki roto i te tūroro.
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 anō 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 mate pukupuku 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.