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Chimeric antigen reseptor (CAR) daawaynta unuggu waxay noqotay daawaynta muhiimka ah ee soo noqnoqda ama dib u soo noqoshada malignancies hematological. Hadda, waxa jira lix badeecooyin auto-CAR T ah oo loo oggolaaday suuqyada Maraykanka, halka ay jiraan afar badeeco CAR-T ah oo ku taxan Shiinaha. Intaa waxaa dheer, noocyo kala duwan oo ah autologous iyo allogeneic CAR-T alaabta ayaa ku hoos jira horumarinta. Shirkadaha dawooyinka ee leh alaabooyinkan soo socda ayaa ka shaqeynaya sidii ay u hagaajin lahaayeen waxtarka iyo badbaadada daaweynta hadda jirta ee cudurrada dhiig-baxa iyada oo la beegsanayo burooyinka adag. Unugyada CAR T ayaa sidoo kale loo sameeyay si ay u daaweeyaan cudurrada aan khatarta ahayn sida cudurrada difaaca jirka.

Qiimaha CAR T waa mid sarreeya (hadda, qiimaha CAR T/CAR ee Mareykanka wuxuu u dhexeeyaa 370,000 iyo 530,000 US dollars, iyo alaabta CAR-T ee ugu jaban Shiinaha waa 999,000 yuan / baabuur). Waxaa intaa dheer, dhacdooyinka sare ee falcelinta sunta daran (gaar ahaan fasalka 3/4 immunoeffector cell-related neurotoxic syndrome [ICANS] iyo cytokine release syndrome [CRS]) waxay noqotay caqabad weyn oo hoos u dhacda - iyo dadka dakhligoodu dhexdhexaadka yahay si ay u helaan daaweynta unugyada CAR T.

Dhawaan, Machadka Teknolojiyadda Hindiya ee Mumbai iyo Mumbai Tata Memorial Hospital oo iskaashanaya si ay u horumariyaan wax soo saarka CD19 CAR T cusub (NexCAR19), waxtarkeedu wuxuu la mid yahay alaabooyinka jira, laakiin badbaadada ka sii wanaagsan, tan ugu muhiimsan waa in qiimaha uu yahay toban-meelood meel oo keliya Maraykanka alaabada la midka ah.

Sida afar ka mid ah lixda daawaynta CAR T ee ay ansixisay Maamulka Cuntada iyo Dawooyinka ee Maraykanka (FDA), NexCAR19 waxa kale oo ay beegsataa CD19. Si kastaba ha ahaatee, badeecooyinka ganacsi ahaan loo oggolaaday ee Maraykanka, jajabka difaaca jirka ee dhammaadka CAR wuxuu caadi ahaan ka yimaadaa jiirarka, kaas oo xaddidaya adkaysigiisa sababtoo ah habka difaaca ayaa u aqoonsanaya shisheeye oo ugu dambeyntii nadiifiyaa. NexCAR19 wuxuu ku daraa borotiinka bini'aadamka dhamaadka jiirka lidka ku ah.

Daraasadaha shaybaadhka ayaa muujiyay in waxqabadka antitumor ee baabuurta "bini'aadamnimada" ay la mid yihiin kuwa ka soo baxa murines-ka, laakiin leh heerarka hoose ee wax soo saarka cytokine. Natiijo ahaan, bukaannadu waxay leeyihiin khatar ah inay yeeshaan CRS daran ka dib markay helaan daawaynta CAR T, taas oo macnaheedu yahay in badbaadada la hagaajiyay.

Si loo yareeyo kharashaadka, kooxda cilmi-baarista NexCAR19 waxay soo saareen, tijaabiyeen oo ku soo saareen badeecada gebi ahaan Hindiya, halkaas oo shaqaaluhu ka jaban yahay waddamada dakhligoodu sarreeyo.
Si loo geliyo CAR unugyada T, cilmi-baarayaashu waxay badanaa isticmaalaan lentivirus-yada, laakiin lentivirus-yadu waa qaali. Dalka Maraykanka, iibsashada fayraska lentiviral ku filan ee tijaabada 50-ka qof ah waxay ku kici kartaa $800,000. Saynisyahano ka tirsan shirkadda horumarinta ee NexCAR19 ayaa iyagu iyagu abuuray gaadiidka hidda-sidaha, iyaga oo si aad ah u yareynaya kharashaadka. Intaa waxaa dheer, kooxda cilmi-baarista Hindiya waxay heleen hab raqiis ah oo ay ku soo saari karaan unugyo farsamaysan, iyaga oo ka fogaanaya isticmaalka mashiinnada iswada ee qaaliga ah. NexCAR19 hadda qiimihiisu waa $48,000 unugkiiba, ama toban meelood meel meel kharashka dhiggiisa Maraykanka. Sida laga soo xigtay madaxa shirkadda soo saartay NexCAR19, qiimaha alaabta ayaa la filayaa in la sii yareeyo mustaqbalka.

Ugu dambeyntii, badbaadada la wanaajiyey ee daaweyntan marka la barbar dhigo alaabada kale ee FDA-ansixisay waxay ka dhigan tahay in bukaannada intooda badani aysan u baahnayn inay ku soo kabtaan qaybta daryeelka degdegga ah ka dib markay helaan daaweynta, sii dhimista kharashka bukaanka.

Hasmukh Jain, oo ah khabiir ku takhasusay kansarka oo ku sugan Xarunta Tata Memorial ee Mumbai, ayaa ka warbixiyay falanqaynta xogta la isku daray ee Wajiga 1 iyo Wajiga 2 ee tijaabooyinka NexCAR19 ee Ururka Bulshada Maraykanka ee Hematology (ASH) 2023 shir sannadeedka.
Tijaabada Wajiga 1 (n = 10) waxay ahayd tijaabo hal xarun ah oo loogu talagalay in lagu tijaabiyo badbaadada 1 × 107 ilaa 5 × 109 CAR T ee qiyaasaha unugyada CAR T ee bukaanada qaba dib-u-soo-noqoshada / refractory fidinta weyn ee B-cell lymphoma (r / r DLBCL), beddelidda lymphoma follicular (tFL), iyo dhexdhexaadiyaha aasaasiga ah ee B-cell lymphoma. Tijaabada Wajiga 2 (n = 50) waxay ahayd hal-gacan, daraasad xarun badan leh oo diiwaan gashan bukaanada ≥15 da'doodu tahay da'da r/r B-unugyada malignancies, oo ay ku jiraan gardarrada iyo qarsoodiga B-cell lymphomas iyo lymphoblastic leukemia ba'an. Bukaannada waxaa la siiyay NexCAR19 laba maalmood ka dib markii ay heleen fludarabine iyo cyclophosphamide. Qiyaasta bartilmaameedku waxay ahayd ≥5×107/kg CAR T unugyada. Halka ugu danbeysa ee ugu danbeysa waxa ay ahayd heerka jawaabta ujeedada (ORR), iyo dhamaadka labaad waxa ka mid ahaa muddada jawaabta, dhacdooyinka xun, badbaadada aan horumarka lahayn (PFS), iyo guud ahaan badbaadada (OS).
Wadarta 47 bukaan ayaa lagu daweeyay NexCAR19, 43 ka mid ah waxay heleen qiyaasta bartilmaameedka. Wadarta 33/43 (78%) bukaan ayaa dhameeyay 28-maalmood qiimaynta faleebada ka dib. ORR waxay ahayd 70% (23/33), kuwaas oo 58% (19/33) ay heleen jawaab celin dhamaystiran (CR). Kooxda lymphoma, ORR waxay ahayd 71% (17/24) iyo CR waxay ahayd 54% (13/24). Kooxda leukemia-ga, heerka CR wuxuu ahaa 66% (6/9, MRD-negative ee 5 xaaladood). Waqtiga daba-galka dhexdhexaadka ah ee bukaanka la qiimayn karo wuxuu ahaa 57 maalmood (21 ilaa 453 maalmood). 3 - iyo 12-bilood oo dabagal ah, dhammaan sagaal bukaan iyo afar-meelood saddex meelood oo bukaan ah ayaa sii waday cafis.
Ma jirin dhimasho la xiriirta daawaynta. Bukaannada midkoodna ma lahayn heer ICANS ah. 22/33 (66%) bukaanada ayaa sameeyay CRS (61% fasalka 1/2 iyo 6% fasalka 3/4). Gaar ahaan, ma jiro CRS ka sarreeya fasalka 3 oo ku jiray kooxda lymphoma. Fasalka 3/4 cytopenia ayaa joogtay dhammaan kiisaska. Muddada dhexdhexaadka ah ee neutropenia waxay ahayd 7 maalmood. Maalintii 28, fasalka 3/4 neutropenia ayaa lagu arkay bukaanada 11/33 (33%) iyo fasalka 3/4 trombocytopenia ayaa lagu arkay bukaanada 7/33 (21%). Kaliya 1 bukaan (3%) ayaa u baahday in la seexiyo qaybta daryeelka degdega ah, 2 bukaan (6%) waxay u baahdeen taageerada vasopressor, 18 bukaan (55%) ayaa helay tolumab, iyada oo dhexdhexaad ah 1 (1-4) iyo 5 bukaan (15%) ayaa helay glucocorticoids. Dhexdhexaadinta joogitaanka waxay ahayd 8 maalmood (7-19 maalmood).
Falanqayntan dhamaystiran ee xogta waxay muujinaysaa in NexCAR19 uu leeyahay waxtarka wanaagsan iyo astaanta badbaadada ee r/r B-cell malignancies. Ma laha ICANS, muddo gaaban oo cytopenia ah, iyo hoos u dhac ku yimaada darajada 3/4 CRS, taas oo ka dhigaysa mid ka mid ah alaabada daaweynta unugyada CD19 CAR T ee ugu badbaadsan. Daawadu waxay gacan ka geysataa hagaajinta sahlanaanta isticmaalka daawaynta unugyada CAR T ee cudurro kala duwan.
Markay ahayd ASH 2023, qoraa kale ayaa ka warbixiyay isticmaalka agabka caafimaadka ee tijaabada wajiga 1/2 iyo kharashyada la xidhiidha daawaynta NexCAR19. Qiyaasta kharashka wax-soosaarka NexCAR19 ee 300 bukaan sannadkii ee qaabka wax-soo-saarka gobollada kala firdhiyey waa ku dhawaad ​​$15,000 bukaankiiba. Cisbitaalka akadeemiyada, celceliska kharashka maaraynta kiliinikada (ilaa dabagalka ugu dambeeya) bukaan kasta waa qiyaastii $4,400 (qiyaastii $4,000 lymphoma iyo $5,565 ee B-ALL). Kaliya 14 boqolkiiba kharashyadan ayaa loogu talagalay joogitaanka isbitaalka.