Umzimba wakho uneentlobo ezahlukeneyo zeeseli zegazi ezimhlophe. Olunye uhlobo, i-lymphocyte , luvela kwiintlobo ezimbini ezibalulekileyo: i-B-cell kunye ne-T-cell. Apha, kumxholo wonyango lomhlaza, sixhalabele kakhulu olo hlobo lwesibini, i-T cell.
Ngoko, yintoni i- receptor receptor (CAR) ye-T-cell yonyango? Ngamafutshane, yindlela yokwelapha ngokukhawuleza ukuba iiprogram ezenzelwe izakhi zee-T ezisele zibe ngcono xa ziqonda kwaye zihlasela umdlavuza ngaphakathi.
Ngenye yeentlobo ezininzi ze-immunotherapi zihlolisiswa. Ukuba unomdla kwi-biotechnology emva kwalolu hlobo lonyango, inkcazelo engakumbi malunga nendlela yokwelapha i-CAR T-cell isebenza ngayo.
Nanku, kugxininiswe kule "zonyango zokuphila" kunye nezinye iindlela zokwelapha ezisebenza ngeT-cell-umzimba wakho we-"soldier system system" -ukulwa nomdlavuza ngokuqaphela nokuhlaselwa kweeseli zesisu. Olunye uhlobo lwezonyango zomhlaza olisebenzisa i-T-cell yakho yomzimba sele luvunyiwe, kwaye abanye kulindeleke ukuba balandele ngokukhawuleza.
Ukwenza iNdlela ngeZonyango ezisekelwe kumzimba
Ukuxubha umzimba wakho omzimba ukuzama ukulwa nomhlaza akuyona into entsha. Enyanisweni, kukho imimiselo yezo zonyango (ezijolise kwimpendulo ye-T-cell) esele yafumana imvume ye-FDA: i-sipuleucel-T, ipilimumab, kunye ne-blinatumomab, ngokomzekelo.
Unyango | Uhlobo lweCarcer | INkqubo yoMzimba |
I-Sipuleucel-T (Nika) | Iimeko ezithile zomhlaza wesifo seprotate |
|
Ipilimumab (Yervoy) | Amanye amatyala enomdlavuza wesikhumba we-melanoma |
|
IBlinatumomab (iBlincyto) | Ukubuyiselwa kwakhona okanye ukukhankanya i-cell-precursor ye-lymphoblastic leukemia (BONKE) kubantu abadala kunye nabantwana |
|
Enye yazo, i-spuleucel-T, izandi kakhulu njenge-CAR cell T-therapy ekubeni isebenzisa iiseli zakho zomzimba eziqokelelwa kuqala kwigazi kunye kwaye zenziwa kwi-laboratory; ziyasebenza kwaye zenziwe ukuba ziphendule ngakumbi kwiiseli zesisu, zize zangenelela kwigazi njengelonyango.
I-Sipuleucel-T ithathwa ngokuba yi-"autologous vaccine", okanye "i-autologous cellular immunotherapy", nangona kunjalo, kwaye ayiyiyo yonyango ye-CAR T-cell ekubeni iiseli ze-immune ziqeqeshelwa ukuphendula, kunokuba ziphathwe ngokusemthethweni ukuze ziphendule iintsholongwane zesisu .
I-immune checkpoint inhibitors ezifana nelilimumab (ngasentla) isebenza ngeendlela ezahlukeneyo zokuzivikela komzimba "zokusebenzisa iibhuleki," okanye "ukubetha i-gas pedal" kwisistim somzimba womzimba, ukuzama ukuvavanya ukuzivikela komzimba wakho ngomdlavuza. Ipilimumab ngumzekelo omnye wonyango osebenza ngale ndlela. Omnye umzekelo we-immune checkpoint inhibitor yi-pembrolizumab (i-Keytruda), ejolise "ekutshintsheni kwe-T-cell" ebizwa ngokuba ngu-PD-1.
I-CAR-T Yonyango: Iinyaniso "Ukuphila kwezidakamizwa"
I-CAR-T zonyango zonyango, nangona kunjalo, kucacile into yazo ehlukileyo. Iifom ze-T zithathwa emzimbeni wakho, zilungiswe ngokwemizimba ukuze ziqonde kakuhle kwaye zibulale amaseli e-tumor, ize iphinde ifakwe njengonyango ophilileyo. Iiseli zinokuveliswa kwaye zikhulile ezincinane iintsuku ezingama-21 kwaye zibuye zibuyele kwigazi.
I-CAR ye-T-cell ityrapy ayilona uhlobo lonyango oluya kusetyenziswa ngaphambi kokuzama ezinye iindlela zonyango-ubuncinane, kungekhona ngoku. Ezi zonyango zonyango zivela ngokugqithiseleyo kwinto ekhohlakeleyo yokuba, kwizigulane ezinezifo zesigaba sexesha elide, unyango lomdlavuza wendabuko, kubandakanya ukuhlinzwa, i-chemotherapy kunye neyeza zonyango, kaninzi zibonelela ngempumelelo.
Ngoko ke, ngoku, ii-CAR-T zonyango zonyango zifumaneke kuphela kwizigulane ezibhalise kwizilingo zonyango, njengoko unyango lubonwa njengophando e-US, kodwa oku kuya kutshintsha ngokukhawuleza. I-CAR-T zonyango zonyango zingagunyazwa yi-FDA kwaye zifumane ngaphandle kwezilingo zeklinikhi kungekudala ngo-2017-2018.
Uluhlu olufutshane lwabaviwa abakhulu abaphuhliswa klinikhi zilandelayo.
CTL019 (tisagenlecleucel) nguNovartis
I-CTL019 yi-CD19-ethile ye-anti-chimeric anti-receptor (i-CAR) -i-T cell cell-based.
Masiqale ngokukhipha isigwebo esandulelayo: i-CD19 yilelekyuli yamaseli athile omzimba abizwa ngokuba yi-B-seli, kwaye ezi iiseli zingabangela iintlobo ezithile ze- leukemia kunye ne-lymphoma .
Inqanaba elilodwa le-CTL019 lilethe ukukhutshwa kwexesha elide kwaye mhlawumbi lonyango (asikwazi okwamanje) kwizikolo ezininzi kwizigulane eziye zaphuma kwiindlela zokonyango.
Nantsi ukuhlaselwa kwezifo apho i-CTL019 iqwalaselwa njengamanje:
- I-CTL019 ifumene utywala lwe-FDA Breakthrough Utyando lwezonyango zokugulisa izigulane zabantu abadala kunye nokutshatyalaliswa kwe-B-cell lymphoma (DLBCL). (Ii-lymphomas zihlala zizigaba ezimbini ezisisiseko: iHodgkin kunye non-Hodgkin. Uhlobo oluqhelekileyo lwe-non-Hodgkin lymphoma yi-DLBCL).
- I-CTL019 iphinda ivunyelwe ukunyangwa kwonyango lokuhlaselwa okanye ukukhusela abantwana kunye nezigulane ezincinci ezindala ezine-B-cell acute lymphoblastic leukemia (ZONKE).
I-CTL019 ifumene ivoti yokuvunyelwana (10-0) engavunyelwanga (imvume ye-10-0) yokuvunywa kwiKomiti yeNgcebiso ngee-Oncologic Drugs Counselling Committee, oku kuthetha ukuba izinto zibukeka zithembise ukuvunyelwa kwayo. I-Novartis ijolise i-CTL019 ukuba iphunyelelwe unyango lwe-B-cell okanye i-B-cell esebenzayo. I-leukemia yinkomfa yesibini yomntwana, kwaye YONKE ifom eqhelekileyo, inoxanduva malunga neepesenti ezingama-25 zobushushu bomsana. Kukho iintlobo ezahlukahlukeneyo ZONKE, kubandakanywa ne-B yeseli NONKE kunye ne-T-cell NONKE, kwaye i-subtypes ngaphakathi iyakuthwala i-propgnoses yayo.
I-CTL019 okwangoku iphantsi kokuphononongwa okuphambili kwaye ukuvunyelwa ngexesha elifanelekileyo kuya kwenza ukuba i-ARV yokuqala ye-CAR-T ifumaneke. Ulwaphulo lwe-T-cell lwe-CAR luya kufumaneka kuphela kwinani elincinci labantwana kunye nabaselula abanomdla we-leukemia abangaphenduliyo kwiinkathalo eziqhelekileyo. Ezi zi gulane zineempembelelo ezimbi, kodwa kuvavanyo oluvakalayo lonyango malunga namazwe angama-12, iipesenti ezingama-83 ezigulane ziye zalahlwa. Ngomnyaka kamva, ezibini kwisithathu zahlala njalo.
Ngenxa yokuba unyango lubhubhisa nje kuphela i-seli ye-B yeeselulu kodwa kunye nempilo ephilileyo, izifo zentsholongwane, izigulane zifuna unyango ukuze zikhuseleke kwiintsholongwane. Bafumana ukunyanzelwa kwe-immune globulins zonke iinyanga ezimbalwa njengendlela yokukhusela.
Enye yeempembelelo eziqhelekileyo zibizwa ngokuba yi-cytokine release syndrome, ebangela imfiva ephezulu kunye neempawu ezifana nezifo ezinokuthi zibe yingozi kangangokuba isigulane siphela ekunyamekelweni okukhulu. Enye into ebaluleke kakhulu yinkxalabo ye-neurotoxicity, enokubangela ukudideka kwesikhashana okanye ukuvuvukala kwengqondo ebulalayo.
Ukuzama ukuqinisekisa ukukhuseleka kwesigulane, i-Novartis ayiyikucwangcisa ukuveliswa komkhiqizo oqhelekileyo, kunye nesicatshulwa sinyanzeliswa ngokubanzi kwaye ngokufutheka kunokwenzeka. Inkampani endaweni yoko izakukhetha amaziko angama-30 ukuya kuma-35 ayeza kunyango. Abaninzi babo bathatha inxaxheba kwilingo lekliniki, kwaye bonke baye bafumana uqeqesho olunzulu.
I-Axicabtagene Ciloleucel nguKite Pharma
Isekelwe eSanta Monica, eCalifornia, iKite Pharma yinkampani egxininisa kwi-CAR kunye ne-T-cell receptor eyenziwe yonyango yolwaphulo. I-Kite iphuhlisa i-CAR ye-T-cell yonyango ebizwa ngokuba yi-axicabtagene ciloleucel, okwangoku iphantsi kokuhlaziywa okusemgangathweni e-US ukwenzela unyango lwezigulane ezine-aggressional non-Hodgkin lymphoma (NHL). Izigulane ezine-NHL ezikhuselayo zijongene nesigidimi esichengileyo kunye nekhefu elingama-50 kuphela lokuhlala ezinyangeni ezintandathu. Oku kugxininisa imfuno yonyango oluphuthumayo kwezi zi gulane.
Njengo-CTL019, i-axicabtagene ciloleucel ijolise i-antigen CD19, iprotheni evezwe kwiseli ye-B-cell lymphomas kunye ne-leukemi. Iiseli ze-T zesigulane zenzelwe ukuvakalisa i-receptor yamachiza ye-antigen (CAR) ukujolisa kwi-antigen CD19.
Kuphuhliso lweziyobisi kunye nenkqubo yokuvunywa, i-axicabtagene ciloleucel ineprofayile efana neyo ye-CTL019, ekugxininiseni kwizonyango ezinemvelaphi ye-B, kodwa i-B yeseli ayibonakali iyincenye yokuphuhliswa kwayo ngeli xesha.
Nantsi ukuhlaselwa kwezifo apho i-axicabtagene ciloleucel ithathelwa ingqalelo ngoku:
- I-Axicabtagene ciloleucel inikwe i-Breakthrough Treatment Status status ye-B-cell lymphoma enkulu (DLBCL), i-follicular lymphoma (TFL), kunye ne-B-cell lymphoma (PMBCL) ephakathi kwe-US FDA kunye ne-Priority Medicines (PRIME). DLBCL kwi-EU.
Ukwamkelwa njengeCandelo loPhulo lwe-FDA luxhaswa ngedatha evela kwi-ZUMA-1 Isigaba sesivivinyo sesi-2 esiye sadibana nesiphelo sokugqibela senqanaba lokuphendula umgomo (ORR) elirekhodwa emva kokunciphisa enye ye-axicabtagene ciloleucel ngama-82 ekhulwini (p <0.0001). Kwimizuzu eyi-8.7 yokulandelelana komzimba, iipesenti ezingama-44 zezigulane zineempendulo eziqhubekayo, ezibandakanya iipesenti ezingama-39 kwizigulane eziphendula ngokupheleleyo (CR).
Iziganeko eziqhelekileyo ezibandakanyekayo ziquka ukupheliswa kwamaseli aphilileyo alwa nokusuleleka kwaye ancedise igazi ukuvala. Njengoko nge-CTL019, enye yezona ziphumo eziqhelekileyo zibizwa ngokuba yi-cytokine release syndrome, ebangela ukukhulelwa komkhuhlane kunye nempawu ezifana nezifo ezinokuthi zibe ziingozi kangangokuba isigulane siphela ekunyamekeleni. I-encephalopathy inokubangela ukudideka kwesikhashana okanye ukuvuvukala kwengqondo ebulalayo. Kwabakho abathathu abafa kulo lonke ixesha lokuvavanywa kwetyala kungekhona ngenxa yokunyuka kwesifo, apho iziganeko ezimbini, zithathwa zihambelana ne-axicabtagene ciloleucel. Kwakhona, ukuphuculwa kweeklinikhi kwezi zi yobisi kulindeleke ukuba ziqhubeke ziqaphele.
I-GoCAR-T, i-Candidate for Tumors Tumors by Bellicum Pharmaceuticals
I-Houston, yaseTexas-esekelwe eBellicum Pharmaceuticals, Inc., inebaviwa bezonyango ezibandakanya i-BPX-601 (i-GoCAR-T, i-tumors eziqinileyo, ezenzelwe ukutshintshwa kweMC yokusebenza ukuphucula ukusebenza, isigaba I), kunye ne-BPX-701 Umgqatswa we-TCR ongapheliyo, kwiimvumi ezomeleleyo , ezenzelwe ukutshintsha kweCaspaCIDe, isigaba I).
Ngoko, oko kuthetha ukuthini? Okubalulekileyo, eli qela lisebenza ekucoceni ubuchwepheshe be-T cell cell ukwenzela ukuba lugcine i-klinikhi ibe namandla okulawula ukuphendula kwe-T cell. Iifom ze-GoCAR-T zenzelwe ukuba zisebenze ngokupheleleyo xa zibonakaliswe kwiiseli zomhlaza kunye ne -agent ebizwa ngokuba yi-rimiducid. Ngoko ke, ngokufanelekileyo, ugqirha uya kuba nako ukulawula izinga lokusebenza kwamaseli ase-CAR ngokuguqula ishedyuli yokulawulwa kwe-rimiducid, kodwa ukubulawa kweeseli kuya kusenzeka ngendlela exhomekeke kuyo.
Abanye abaviwa
UJuno yinkampani ngoku ijolise kwiJCAR017, umkhiqizo we-CAR-T ojolise kwiCD19. UJuno ukhangele ukufumana i-JCAR017 kwimarike ngo-2018 kwiNHL. Inkampani ihlangene neCelgene kule mizamo.
IZIMPHARM I-Oncology inomkhiqizo othile we-CD19 kwaye isebenza kwi-CAR ekhethekileyo ye-CAR T-cell yonyango ye-lemonemic acute leememiaid (AML). I-NantKwest yinkampani ye-immunotherapy egxile ekusebenziseni umbulali wemvelo (NK) amaseli ukunyanga umdlavuza, izifo ezithathelwanayo kunye nezifo ezivuthayo.
Isakhelo se-NK yenkampani esekelwe ekwenzeni iseli ukufa kumhlaza okanye amangqamuzana asulelekileyo ngeendlela ezintathu ezahlukeneyo zokubulala-ngokubulala ngqo usebenzisa i-cell cell NK (i-NN); Ukubulawa kwabantu abasebenzisa i-anti-anti-mediated killers ngokusebenzisa i-haNKs, kunye nokubulawa okubanjelwe ngokusetyenziswa ngokusetyenziswa kweTNNs.
ILizwi
Ezinye zeziphumo zakuqala zonyango lwe-CAR-T ziye zavuya kakhulu, zinika imithi emitsha kumaqela ezigulane ezingakaze zinezo zikhetho ngaphambili. Kukho kwakhona ukungaphumeleli, nangona kunjalo, kunye neengxaki ezinzima zokubangela ukuba ezi zonyango ziphumelele ngokusemgangathweni kunye nenani elincinci letyhefu.
Njengoko abaphandi bafunda okungakumbi malunga nokuphendula komzimba okuxhatshazwayo kule miba, kunye nefuthe kwiimpawu ezijoliswe kuyo, umfanekiso ocacileyo weengozi kunye neenzuzo kufuneka zivele.
> Imithombo:
> Wang M, Yin B, Wang HY, Wang RF. Ukuqhubeka kwangoku kwi-T-cell-based immunotherapy. Immunotherapy . 2014; 6 (12): 1265-1278.
> Bhoj VG, Arhontoulis D, Wertim G, et al. Ukunyamezela kweeseli zeplasma ezihlala ixesha elide kunye nokuzikhusela komntu ngokuziphendulela kwi-CD19 ejoliswe kwi-CAR T-cell therapy. Igazi. 2016; 128 (3): 360-370.
> I-Kite ifumana ukuhlolwa kokuPhambili kwe-Axicabtagene Ciloleucel yase-US. http://ir.kitepharma.com/releasedetail.cfm?releaseid=1028075 Ifumaneka ngoJulayi 2017.
> Morris EC, Stauss HJ. Ukuphucula i-T-cell ye-gene receptor therapy ye-hematologic malignancies. Igazi . 2016; 127 (26): 3305-3311.
> Ipaki JH, Geyer MB, Brentjens RJ. I-CD19-ejoliswe kwi-CAR T-cell therapeutics yezilwanyana zesifo se-hematologic: ukutolika iziphumo zekliniki kuze kube yimhla. Igazi . 2016; 127 (26): 3312-3320.