Mhlawumbe amasosha omzimba aletha engqondweni yezithombe zamangqamuzana egazi ezimhlophe ezigcoba kuma-bacteria, noma ama-antibodies ahlasele umhlasela-angamavikeli omzimba wakho ngokumelene nama-bacterium kanye nama-virus angakwenza ugule. Kodwa-ke, amasosha omzimba ayaziwa ngokukwazi kwawo ukuthola, ukufuna nokubhubhisa amaseli omdlavuza.
Ngamandla anjalo njengamasosha omzimba, kudingeke kube yindlela yokudayela izinto phansi kwe-notch ukuze amaseli avamile, anempilo ahlaselwe ngephutha.
Ngenhlanhla, isimiso somzimba sokuzivikela siklanyelwe ngalezi zivivinyo zokuphepha endaweni. Kodwa-ke, amangqamuzana omdlavuza, avela kumaseli ayekade ejwayelekile, ngezinye izikhathi angasebenzisa lokhu kuhlolwa kokuphepha ukuze kuzuze ukuhlaselwa yisistimu yomzimba. Lezi zivivinyo zokuphepha (izingqimba, empeleni) ziyaziwa ngokwesayensi njengama- checkpoints immune , kanti izidakamizwa ezithatha ama-checkpoints ziyi-inhibitors yokuhlola.
I-Immune Checkpoints
Njengezinqubo ezibucayi ebhizinisini nasezinkambweni zomzimba, isinqumo somzimba sokushisa impendulo yegciwane lengculaza ngokuvamile sidinga "ukusayinwa" okuningi futhi "kuvunyelwe" ngaphambi kokuba amasondo abekwe ukunyakaza-umnyango ngamunye ungenza noma awukwazi ukuthwala isisindo esifanayo nesinye umnyango awuqambi ukuthi isinqumo sinqunywe.
Ngakho-ke, izivikelo eziningana eziyinkimbinkimbi zisiza ukugcina isimiso somzimba sokuzivikela singathinteki kumuntu ongummpi wangaphandle noma ukuphutha ingxenye "ye-self" ye-invader eyingozi. Lezi zivikelo zingasetshenziswa ngokucophelela ngamangqamuzana omdlavuza ukuze ugweme ukutholakala kwamagciwane kodwa futhi angaxoshwa ngabakhiqizi bezidakamizwa ukuze bahlubule amangqamuzana omdlavuza ukuze bangabe "bengabonakali" esimisweni somzimba sokuzivikela .
Lesi sinqumo sebhizinisi se-biologic sokukhulisa indlela yokuzivikela ngomzimba ngezinye izikhathi kubalulekile kuhilela ukusebenzisana "nomnyango wesifo sokufa" -ukuthi, uhlelo lokufa 1 oluhleliwe (PD-1) olulawula izimpendulo zokuvuvukala kwezicubu.
I-Checkpoint Inhibitors YimiDakamizwa Yokusiza Amaseli E-T Thola Imiyalo Yokumaketha
Umzila we-PD-1 une "umugqa oqondile" kuma-T-cell, amasosha omzimba aphuma abulale amangqamuzana omdlavuza; Kodwa-ke, akude neze into eqinisekile ukuthi amasosha e-T-cell azozihlela, ahlele ngaphambili, aqale ukubhubhisa amaseli omdlavuza.
Kungenxa yokuthi enye iminyango nayo ineziphakamiso kuma-T-cells nemisebenzi yabo. Kunezinkomba eziningi okumelwe zenzeke ngaphambi kokuba amasosha athole ama-oda azo.
Enye yezinto ezinquma ukuthi ngabe imiyalo yokuhamba inikezwa yamukeli we-PD1, osebenzela uhlobo olufana nomuntu ovelele kulolu chungechunge lomyalo. "Abacebisi" ababili kulokhu okujwayelekile okucebisa ngokuqinile ukumemezela impi ngamangqamuzana omdlavuza kuyi-PDL-1 ne-PDL-2. Laba beluleki be-anti-war, i-PDL-1 ne-PDL-2, empeleni ama-molecule ahlanganisa ama-PD1 receptors kuma-T-cell. Uma bebopha basitshela ama-T-cells ukuthi ahlale phansi, angenayo imiyalo yokuhamba ngokumelene nomdlavuza.
Amaseli E-Cancer Azama Ukusabalalisa Amandla "Abacebisi Abaphikisana Nempi"
Ngezinye izikhathi amangqamuzana omdlavuza enza abeluleki abaningi bokulwa nempi, ngokwabo. Omunye noma kokubili we-PD-L1 no-PD-L2, kumaseli ezinhlakeni, kuhlanganise namaseli omdlavuza, angabophela ama-PD1 receptors kuma-T-cells futhi avimbele umsebenzi wabo.
Ukuvimbela lokhu kuhlangana phakathi kwe-PD-1 kuma-T-amaseli nabadlali bayo ababili, abangaphandle kwamanye amaseli, kungaholela ekusebenzeni okunamandla kwamaseli e-T, kanye nochungechunge lwezenzakalo eziholela ekuphenduleni okusheshayo okuvuvukala.
Ukwelapha Okubhekiswe PD-1 noma PD-L1
Amanye amangqamuzana omdlavuza enza inani elikhulu le-PD-L1, elisiza ukuba babalekele ukuhlaselwa komzimba.
Abacwaningi bezokwelapha izidakamizwa bangenza ukwelashwa kwe-antioclonal anti-antibody okubhekiswe kumbekeli we-PD-1 (jikelele) noma i-ligand ye-PD-L1 (umeluleki wezempi) ukuze kukhulunywe ukumelana nomzimba ngokumelene namangqamuzana omdlavuza, futhi asetshenziselwe ukwelapha okuthile ukwelapha.
Ekuqaleni, impumelelo yabonakala ngezicubu eziqinile, kodwa manje lezi zihloswe zihlolisiswa nge-cancer ye-hematologic, noma i- blood cancers , kanye ne-leukemia, i-lymphoma ne-myeloma. E-classic Hodgkin lymphoma, kwanda ukukhiqizwa kwe-PD-1 ligand (PD-L1 / 2) emangqamuzaneni omdlavuza ngakho-ke kunethemba lokuthi ukukhubazeka kwe-Hodgkin lymphoma kuya ekuvinjeni kwe-PD-1.
Njengoba lezi zindlela zokwelapha zithuthukisa isimiso somzimba sokuzivikela ngokususa ezinye zokuphepha kwayo, kunokukhathazeka ukuthi lokhu kungaholela ekulimazeni amangqamuzana aphilile nemiphumela emibi kwabanye abantu. Izenzakalo ezimbi ezivame ukuhlotshaniswa nama-antibodies okuvimbela i-PD-1 zihlanganisa ukulimala, ukushayeka, nokuhuda. Ngaphansi kaningi kungabangela izinkinga ezingathí sina emaphashini, emathunjini, isibindi, izinso, izigulane zokwenza amahomoni, noma ezinye izitho.
Ezinye izindlela zokwelashwa ezibhekiswe ku-PD-1 noma i-PD-L1 manje zivivinywa ekuvivinyweni kwemithi, kokubili zodwa futhi zihlangene nezinye izidakamizwa. Kunezimbalwa kuphela zokwelapha ezitholwe imvume ye-FDA ukuze isetshenziswe umdlavuza kuze kube manje, kodwa abanye abaningi manje bafundiswa ekuvivinyweni kwemitholampilo. Njengoba ucwaningo luqhubeka, sizoqonda kangcono uhlelo nokuthi singayithola kanjani.
> Imithombo:
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I-Pardoll DM. Ukuvimbela ukuhlolwa kwamagciwane okulwa nomdlavuza we-immunotherapy. I-Can Rev Cancer. 2012; 12 (4): 252-64.
U-Romano E, uRomero P. Isithembiso sokwelapha sokuphazamisa ukuhlolwa kwamagciwane e-PD-1 / PD-L1 emdlalweni: ukukhipha umsebenzi we-CD8 T cell mediated anti-tumor imiphumela ekusebenzeni okuphawulekayo, okungakaze kube khona emitholampilo ehlukahlukene. J Ngomunye Umdlavuza . 2015; 3: 15.
I-American Cancer Society. I-inhibitors yokuhlola i-Immune ukuphatha umdlavuza.