amakuru

Chimeric antigen reseptor (CAR) T ivura ingirabuzimafatizo yabaye ubuvuzi bwingenzi bwo kuvura indwara mbi ziterwa no kuvura indwara. Kugeza ubu, hari ibicuruzwa bitandatu by’imodoka-CAR T byemewe ku isoko muri Amerika, mu gihe hari ibicuruzwa bine CAR-T byanditswe mu Bushinwa. Mubyongeyeho, ibicuruzwa bitandukanye bya autologique na allogeneic CAR-T biri gutezwa imbere. Uruganda rwa farumasi hamwe nibicuruzwa bizakurikiraho birakora kugirango tunoze imikorere numutekano wubuvuzi buriho kuburwayi bwa hematologiya mugihe byibasiye ibibyimba bikomeye. CAR T nayo irimo gutezwa imbere kuvura indwara zitari mbi nkindwara ziterwa na autoimmune.

Igiciro cya CAR T ni kinini (kuri ubu, igiciro cya CAR T / CAR muri Amerika kiri hagati y’amadolari 370.000 na 530.000 by’amadolari y’Amerika, naho ibicuruzwa bya CAR-T bihendutse mu Bushinwa ni 999.000 Yuan / imodoka). Byongeye kandi, umubare munini w’ibibazo by’uburozi bukabije (cyane cyane icyiciro cya 3/4 immunoeffector selile ifitanye isano na syndrome ya neurotoxic syndrome [ICANS] na syndrome ya cytokine irekura [CRS]) byahindutse imbogamizi ikomeye kubantu bo hasi - kandi binjiza amafaranga yo kwivuza CAR T.

Vuba aha, Ishuri Rikuru ry’ikoranabuhanga ry’Ubuhinde Mumbai n’ibitaro by’Urwibutso rwa Mumbai Tata ku bufatanye bwo guteza imbere ibicuruzwa bishya bya CD19 CAR T (NexCAR19), imikorere yacyo isa n’ibicuruzwa bihari, ariko umutekano mwiza, icy'ingenzi ni uko ikiguzi ari kimwe cya cumi gusa muri Amerika ibicuruzwa bisa.

Kimwe na bine muri bitandatu CAR T ivura byemejwe n’ikigo cy’Amerika gishinzwe ibiryo n’ibiyobyabwenge (FDA), NexCAR19 nayo yibasira CD19. Nyamara, mubicuruzwa byemewe mubucuruzi muri Reta zunzubumwe zamerika, agace ka antibody kumpera ya CAR ubusanzwe kava ku mbeba, ibyo bikagabanya gukomera kwayo kuko sisitemu yubudahangarwa yemera ko ari umunyamahanga kandi amaherezo ikabikuraho. NexCAR19 yongeramo poroteyine yumuntu kurangiza antibody yimbeba.

Ubushakashatsi bwa laboratoire bwerekanye ko ibikorwa bya antitumor yimodoka "zabantu" bigereranywa n’imodoka zikomoka kuri murine, ariko hamwe n’urwego rwo hasi rw’umusemburo wa cytokine. Kubera iyo mpamvu, abarwayi bafite ibyago byo kwandura CRS nyuma yo guhabwa imiti ya CAR T, bivuze ko umutekano wateye imbere.

Kugira ngo ibiciro bigabanuke, itsinda ry’ubushakashatsi rya NexCAR19 ryateje imbere, ripima kandi rikora ibicuruzwa mu Buhinde, aho umurimo uhendutse kuruta mu bihugu byinjiza amafaranga menshi.
Kugirango winjize CAR muri selile T, abashakashatsi mubisanzwe bakoresha lentivirus, ariko lentivirus irazimvye. Muri Reta zunzubumwe zunzubumwe zunzubumwe zunzubumwe zunzubumwe zunzubumwe zunzubumwe zunzubumwe zunzubumwe zunzubumwe zunzubumwe zunzubumwe zunzubumwe zunzubumwe zunzubumwe zunzubumwe zunzubumwe zunzubumwe zamerika, kugura ibice bihagije bya lentiviral kubigeragezo byabantu 50 bishobora gutwara $ 800,000. Abahanga mu kigo cyiterambere cya NexCAR19 bakoze imodoka yo gutanga gene ubwabo, bigabanya cyane ibiciro. Byongeye kandi, itsinda ry’ubushakashatsi mu Buhinde ryabonye uburyo buhendutse bwo gukora ingirabuzimafatizo nyinshi, birinda gukoresha imashini zihenze. Kugeza ubu NexCAR19 igura amadolari 48.000 kuri buri gice, cyangwa icya cumi cyigiciro cya mugenzi wacyo muri Amerika. Nk’uko byatangajwe n'umuyobozi w'ikigo cyateje imbere NexCAR19, biteganijwe ko igiciro cy'ibicuruzwa kizagabanuka kurushaho mu gihe kiri imbere.

Hanyuma, umutekano wokuvura ugereranije nibindi bicuruzwa byemewe na FDA bivuze ko abarwayi benshi badakeneye gukira mubitaro byita ku barwayi nyuma yo kuvurwa, bikagabanya amafaranga y’abarwayi.

Hasmukh Jain, inzobere mu buvuzi bw’ubuvuzi mu kigo cy’Urwibutso rwa Tata i Mumbai, yatangaje ko isesengura ry’amakuru ryakozwe mu cyiciro cya 1 n’icyiciro cya 2 cy’iburanisha rya NexCAR19 mu nama ngarukamwaka y’Abanyamerika y'Abanyamerika (ASH) 2023.
Ikizamini cya Phase 1 (n = 10) cyari ikigeragezo kimwe cyagenewe gupima umutekano wa dosiye ya selile 1 × 107 kugeza 5 × 109 CAR T ku barwayi bafite lymphoma nini ya B-selile (r / r DLBCL), ihindura lymphoma follicular (tFL), na lymphoma nini yo hagati (PMBCL). Ikigeragezo cyo mu cyiciro cya 2 (n = 50) cyari ubushakashatsi bumwe, ukuboko kwinshi kwandikishije abarwayi bafite imyaka 15 y'amavuko bafite indwara mbi ya r / r B, harimo na lymphoma B-selile ikaze ndetse nubupfumu na lymphoblastique ikaze. Abarwayi bahawe NexCAR19 nyuma yiminsi ibiri bakiriye fludarabine wongeyeho cyclophosphamide. Igipimo cyagenewe cyari ≥5 × 107 / kg CAR T selile. Iherezo ryibanze ryari igipimo cyibisubizo (ORR), naho amaherezo ya kabiri yarimo igihe cyo gusubiza, ibintu bibi, kubaho nta terambere ryabaho (PFS), no kubaho muri rusange (OS).
Abarwayi 47 bose bavuwe na NexCAR19, 43 muri bo bakaba barahawe igipimo cyagenwe. Abarwayi 33/43 (78%) barangije isuzuma ryiminsi 28 nyuma yo gushiramo. ORR yari 70% (23/33), muri bo 58% (19/33) babonye igisubizo cyuzuye (CR). Muri lymphoma cohort, ORR yari 71% (17/24) na CR yari 54% (13/24). Muri cohort ya leukemia, igipimo cya CR cyari 66% (6/9, MRD-mbi mubibazo 5). Igihe cyo gukurikirana hagati yabarwayi basuzumwa cyari iminsi 57 (iminsi 21 kugeza 453). Mugihe cy'amezi 3 - n'amezi 12, abarwayi icyenda bose hamwe na bitatu bya kane by'abarwayi bakomeje gukira.
Nta mpfu zatewe no kwivuza. Nta n'umwe mu barwayi wari ufite urwego urwo ari rwo rwose rwa ICANS. 22/33 (66%) abarwayi bagize CRS (61% icyiciro cya 1/2 na 6% icyiciro cya 3/4). Ikigaragara ni uko nta CRS iri hejuru yicyiciro cya 3 yari ihari muri lymphoma cohort. Icyiciro cya 3/4 cytopenia yari ihari mubibazo byose. Igihe cyo hagati ya neutropenia cyari iminsi 7. Ku munsi wa 28, icyiciro cya 3/4 neutropenia cyagaragaye ku barwayi 11/33 (33%) naho icyiciro cya 3/4 trombocytopenia cyagaragaye ku barwayi 7/33 (21%). Umurwayi 1 gusa (3%) ni we wasabye kwinjira mu gice cyita ku barwayi bakomeye, abarwayi 2 (6%) basabye inkunga ya vasopressor, abarwayi 18 (55%) bahawe tolumab, hamwe n’umuhuza wa 1 (1-4) naho abarwayi 5 (15%) bakiriye glucocorticoide. Uburebure bwo hagati bwo kumara iminsi 8 (iminsi 7-19).
Isesengura ryuzuye ryamakuru ryerekana ko NexCAR19 ifite imikorere myiza numwirondoro wumutekano muri r / r B-selile mbi. Ntabwo ifite ICANS, igihe gito cya cytopenia, hamwe no kugabanuka kwicyiciro cya 3/4 CRS, bigatuma iba kimwe mubicuruzwa byica CD19 CAR T bifite umutekano. Umuti ufasha kunoza uburyo bworoshye bwo gukoresha imiti ya CAR T mu ndwara zitandukanye.
Muri ASH 2023, undi mwanditsi yatanze raporo ku mikoreshereze y’ubuvuzi mu cyiciro cya 1/2 n’amafaranga ajyanye no kuvura NexCAR19. Ikigereranyo cy’umusaruro wa NexCAR19 ku barwayi 300 ku mwaka mu buryo bwo gukwirakwiza umusaruro mu karere ni amadorari 15,000 kuri buri murwayi. Mu bitaro byigisha, impuzandengo yo gucunga amavuriro (kugeza kubikurikiranwa bwa nyuma) kuri buri murwayi ni amadorari 4.400 (hafi 4000 $ ya lymphoma na 5.565 $ kuri B-BYOSE). Ibice 14 kw'ijana gusa muribi biciro ni kubitaro.