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Chimeric antigen receptor (CAR) T cell far ya zama wani muhimmin magani ga maimaitawa ko refractory hematological malignancies. A halin yanzu, akwai samfuran auto-CAR T guda shida da aka amince da su don kasuwa a Amurka, yayin da akwai samfuran CAR-T guda huɗu da aka jera a China. Bugu da kari, nau'ikan samfuran autologous da allogeneic CAR-T suna ƙarƙashin haɓakawa. Kamfanonin harhada magunguna tare da waɗannan samfuran na gaba suna aiki don haɓaka inganci da amincin hanyoyin da ake amfani da su don cutar cututtukan jini yayin da suke yin niyya mai ƙarfi. Hakanan ana haɓaka ƙwayoyin CAR T don magance cututtukan da ba su da haɗari kamar cututtukan autoimmune.

Farashin CAR T yana da yawa (a halin yanzu, farashin CAR T/CAR a Amurka yana tsakanin dalar Amurka 370,000 zuwa 530,000, kuma samfuran CAR-T mafi arha a China sun kai yuan 999,000). Bugu da ƙari, babban abin da ya faru na mummunan halayen haɗari (musamman sa 3/4 immunoeffector cell-related neurotoxic syndrome [ICANS] da cytokine release syndrome [CRS]) ya zama babban cikas ga ƙananan - da masu shiga tsakani don karɓar maganin CAR T.

Kwanan nan, Cibiyar Fasaha ta Indiya Mumbai da Mumbai Tata Memorial Hospital tare da haɗin gwiwar haɓaka sabon samfurin CD19 CAR T (NexCAR19), ingancinsa yayi kama da samfuran da ake dasu, amma mafi kyawun aminci, mafi mahimmanci shine farashin shine kawai kashi ɗaya cikin goma na samfuran makamancin Amurka.

Kamar hudu daga cikin hanyoyin kwantar da tarzoma na CAR T shida da Hukumar Abinci da Magunguna ta Amurka (FDA) ta amince da su, NexCAR19 kuma yana kaiwa CD19 hari. Koyaya, a cikin samfuran da aka amince da kasuwanci a cikin Amurka, gutsuttsuran rigakafin mutum a ƙarshen CAR yawanci yana fitowa ne daga beraye, wanda ke iyakance dagewar sa saboda tsarin garkuwar jiki ya gane shi a matsayin na waje kuma a ƙarshe yana share shi. NexCAR19 yana ƙara furotin ɗan adam zuwa ƙarshen antibody linzamin kwamfuta.

Nazarin dakin gwaje-gwaje ya nuna cewa aikin antitumor na Motoci na "humanized" yana kama da na motocin da aka samu daga murine, amma tare da ƙananan matakan samar da cytokine. A sakamakon haka, marasa lafiya suna da raguwar haɗarin haɓakar CRS mai tsanani bayan sun karbi maganin CAR T, wanda ke nufin cewa an inganta tsaro.

Don rage farashi, ƙungiyar bincike ta NexCAR19 ta haɓaka, gwadawa da kera samfurin gaba ɗaya a Indiya, inda aiki ya fi arha fiye da na ƙasashe masu samun kuɗi.
Don shigar da CAR cikin ƙwayoyin T, masu bincike yawanci suna amfani da lentiviruses, amma lentivirus suna da tsada. A Amurka, siyan isassun magungunan lentiviral don gwajin mutum 50 na iya kashe $800,000. Masana kimiyya a kamfanin ci gaba na NexCAR19 ne suka kirkiro motar isar da kwayoyin halitta da kansu, suna rage tsada sosai. Bugu da ƙari, ƙungiyar masu bincike ta Indiya sun sami hanya mai rahusa don samar da ƙwayoyin injiniyoyi masu yawa, da guje wa amfani da na'urori masu sarrafa kansu masu tsada. NexCAR19 a halin yanzu yana kashe kusan $48,000 kowace raka'a, ko kashi goma na farashin takwaransa na Amurka. A cewar shugaban kamfanin da ya haɓaka NexCAR19, ana sa ran za a ƙara rage farashin samfurin nan gaba.

A ƙarshe, ingantaccen amincin wannan magani idan aka kwatanta da sauran samfuran da aka yarda da FDA yana nufin cewa yawancin marasa lafiya ba sa buƙatar murmurewa a cikin sashin kulawa mai zurfi bayan sun karɓi magani, yana ƙara rage farashin marasa lafiya.

Hasmukh Jain, masanin ilimin likitancin likitanci a Cibiyar Tunawa ta Tata a Mumbai, ya ba da rahoton hadahadar bayanai game da gwaji na Phase 1 da Phase 2 na NexCAR19 a taron shekara-shekara na American Society of Hematology (ASH) 2023.
Gwajin 1 na Phase (n = 10) gwaji ne na tsakiya guda ɗaya wanda aka tsara don gwada lafiyar 1 × 107 zuwa 5 × 109 CAR T kwayoyin halitta a cikin marasa lafiya tare da relapsed / refractory yaduwa babban lymphoma B-cell (r / r DLBCL), yana canza lymphoma follicular (tFL), da kuma babban mediastinal babban B-cell lymphoma (P. Gwajin 2 na Phase (n = 50) wani nau'i ne na hannu guda ɗaya, binciken multicenter wanda ya sanya marasa lafiya ≥15 shekaru tare da r / r B-cell malignancies, ciki har da m da occult B-cell lymphomas da m lymphoblastic cutar sankarar bargo. An bai wa marasa lafiya NexCAR19 kwanaki biyu bayan sun sami fludarabine da cyclophosphamide. Adadin da aka yi niyya shine ≥5 × 107/kg CAR T Kwayoyin. Maƙasudin ƙarshe na farko shine ƙimar amsawar haƙiƙa (ORR), kuma ƙarshen ƙarshe na biyu ya haɗa da tsawon lokacin amsawa, abubuwan da ba su da kyau, tsira mara ci gaba (PFS), da rayuwa gabaɗaya (OS).
An yi wa marasa lafiya 47 magani tare da NexCAR19, 43 daga cikinsu sun sami adadin da aka yi niyya. Jimlar marasa lafiya na 33/43 (78%) sun kammala kima na kwanaki 28 bayan jiko. ORR ya kasance 70% (23/33), wanda 58% (19/33) ya sami cikakkiyar amsa (CR). A cikin ƙungiyar lymphoma, ORR ya kasance 71% (17/24) kuma CR ya kasance 54% (13/24). A cikin ƙungiyar cutar sankarar bargo, ƙimar CR ya kasance 66% (6/9, MRD-korau a cikin lokuta 5). Matsakaicin lokacin bin diddigin majinyata masu ƙima shine kwanaki 57 (kwanaki 21 zuwa 453). A 3 - da 12 watanni masu biyowa, duk marasa lafiya tara da kashi uku cikin hudu na marasa lafiya sun kiyaye gafara.
Babu mace-mace masu nasaba da jiyya. Babu wani daga cikin marasa lafiya da ke da kowane matakin ICANS. 22/33 (66%) marasa lafiya sun haɓaka CRS (61% grade 1/2 da 6% grade 3/4). Musamman ma, babu CRS sama da aji 3 da ya kasance a cikin ƙungiyar lymphoma. Sashi 3/4 cytopenia ya kasance a duk lokuta. Tsawon tsaka-tsakin neutropenia shine kwanaki 7. A ranar 28, an lura da neutropenia na 3/4 a cikin marasa lafiya 11/33 (33%) kuma an lura da 3/4 thrombocytopenia a cikin marasa lafiya na 7/33 (21%). Mai haƙuri 1 kawai (3%) ya buƙaci shiga cikin sashin kulawa mai zurfi, marasa lafiya 2 (6%) suna buƙatar tallafin vasopressor, marasa lafiya 18 (55%) sun karɓi tolumab, tare da matsakaici na 1 (1-4) da marasa lafiya 5 (15%) sun sami glucocorticoids. Tsawon tsaka-tsakin zama shine kwanaki 8 (kwanaki 7-19).
Wannan cikakken bincike na bayanai yana nuna cewa NexCAR19 yana da ingantaccen inganci da bayanin martaba a cikin r/r B-cell malignancies. Ba shi da ICANS, ɗan gajeren lokaci na cytopenia, da ƙarancin abin da ya faru na aji 3/4 CRS, yana mai da shi ɗayan mafi aminci samfuran CD19 CAR T. Maganin yana taimakawa wajen inganta sauƙin amfani da maganin CAR T a cikin cututtuka daban-daban.
A ASH 2023, wani marubucin ya ba da rahoto game da amfani da albarkatun likita a cikin gwaji na 1/2 da kuma farashin da ke da alaƙa da jiyya na NexCAR19. Kimanin farashin samarwa na NexCAR19 a marasa lafiya 300 a kowace shekara a cikin tsarin samarwa da aka tarwatsa kusan $15,000 ga kowane majiyyaci. A asibitin ilimi, matsakaicin farashin kulawar asibiti (har zuwa na ƙarshe) kowane mai haƙuri shine kusan $ 4,400 (kimanin $ 4,000 na lymphoma da $ 5,565 don B-ALL). Kusan kashi 14 cikin ɗari na waɗannan kuɗaɗen na zaman asibiti ne.