May 2023: Chimeric antigen receptor (CAR) T-cell therapy is an innovative development in the field of individualized cancer therapy. The patient’s own T-cells are genetically modified during the manufacturing process to express a synthetic receptor that binds to a tumour antigen. The patient’s body is then infused with CAR T-cells that have been grown for clinical usage and are ready to fight cancer cells. Even though CAR T-cell therapy is regarded as a significant advancement in cancer immunotherapy, it is not without drawbacks.
Chimeric antigen receptor T-cell (CAR T-cell) therapy is a ground-breaking component in the treatment of hematologic malignancies. Six CAR T-cell therapies have currently been approved by the US Food and Drug Administration (US FDA) (axicabtagene ciloleucel, brexucabtagene autoleucel, idecabtagene vicleucel, lisocabtagene maraleucel, tisagenlecleucel, and ciltacabtagene autoleucel), but only one (tisa-cel) is offered in Korea. In this study, we talk about the difficulties and obstacles that CAR T-cell treatment is now facing in Korea, such as the difficulties with patient accessibility, cost, and reimbursement.
2021 yilda ko‘plab koreys korxonalari CAR-T terapiyasini rivojlantirishga kirishdilar. Sanoat insayderlarining ta'kidlashicha, mahalliy biofarmatsevtika kompaniyalari Novartisning CAR-T terapiyasi (ingrediyent: tisagenlecleucel) mahalliy ma'qullanishidan hayajonlangan.
Immunologik T hujayralariga kimerik antigen retseptorlarini kiritish orqali CAR-T terapiyasi saraton hujayralariga qaratilgan hujayra terapiyasining bir turi hisoblanadi. Ajoyib javob tezligi tufayli u ba'zan "mo''jizaviy antikanser dori" deb ataladi.
Uni ishlab chiqarish mashaqqatli jarayon bo'lib, bemorning T hujayralarini kasalxonada to'plash va ularni yaxshi ishlab chiqarish amaliyotiga (GMP) rioya qiladigan muassasada etishtirishni o'z ichiga oladi.
CAR T-Cell ishlab chiqarish va boshqarish jarayoni
Tisa-cel, Koreyadagi yagona tijorat litsenziyasiga ega CAR T-hujayra mahsuloti, bemordan T-hujayra donatsiyasidan oldin leykaferez operatsiyalarini talab qiladigan avtolog shaxsiylashtirilgan uyali terapiya. Ushbu hujayralarni ishlab chiqarish keyinchalik litsenziyalangan ishlab chiqarish korxonalariga (boshqa yarim sharlarda) topshiriladi. Tayyor mahsulotlar ishlab chiqarish va sifatini tekshirishdan so'ng bemorni infuzion qilish uchun shifoxonalarga yuboriladi [2]. Bemorlar boshqaruv texnikasi va CAR T-hujayralarini ishlab chiqarishning murakkabligi tufayli katta to'siqlarga duch kelishadi. Cheklangan ishlab chiqarish maydonlari keyingi jarayonlarning bajarilishiga to'sqinlik qilishi mumkin, chunki ishlab chiqarish ishlab chiqaruvchilarning ishchi kuchiga juda bog'liq, ta'minot zanjiri uzilishlari ba'zan kutilmagan kechikishlarga olib keladi.
Akkreditatsiyadan o'tgan CAR T-hujayralarini davolash vositalarining yo'qligi bemorlarga kirish imkoniyati bilan bog'liq yana bir muhim muammodir. CAR T-hujayralarini davolash allaqachon ko'p resurslarni sarflaydi, chunki u ko'plab yuqori malakali mutaxassislarni va ishonchli infratuzilmani talab qiladi [3]. Reanimatsiya bo'limiga, leykaferez bo'limiga, hujayralarni etarli darajada saqlashga, o'tkir muammolarni rivojlanayotgan bemorlarni kuzatish va boshqarish uchun belgilangan protokollarga ega tuzilgan klinik bo'limga va yaxshi tashkil etilgan ish joylariga ega klinik bo'limga ehtiyoj bor. Gematologlar, jiddiy tibbiy yordam bo'yicha ixtisoslashgan tibbiyot mutaxassislari, nevrologlar va malakali hamshiralar doimiy ravishda tibbiy xodimlarga muhtoj. Koreya oziq-ovqat va dori xavfsizligi vazirligi, shuningdek, "ilg'or regenerativ tibbiyot va ilg'or biologik mahsulotlar xavfsizligi va qo'llab-quvvatlash to'g'risidagi akt" va "to'g'risidagi aktning kuchga kirishi to'g'risida"gi qarorga muvofiq CAR T-hujayra terapiyasini taqdim etishni rejalashtirayotgan barcha markazlarni baholashi kerak. ilg'or regenerativ tibbiyot va ilg'or biologik mahsulotlar xavfsizligi va ularni qo'llab-quvvatlash" [4]. Natijada, Seul jismoniy jihatdan Koreyaning CAR T-hujayrali terapiya muassasalarining ko'pchiligiga ega bo'lib, mavjud cheklovlarga qo'shimcha qiladi.
Koreyada yuqori xarajat va CAR T-Cell terapiyasi ishlab chiqarish
Ko'pmillatli farmatsevtika kompaniyalari tomonidan ishlab chiqilgan dori-darmonlarning yuqori narxi koreyslik bemorlarga undan foydalanishni qiyinlashtiradi. Natijada, Koreya korxonalari ushbu muammolarni hal qilish maqsadida CAR-T muolajalarini yaratdilar va mahalliylashtirdilar. Ko'pgina korxonalar CAR-T terapiyasini ishlab chiqishni boshladilar yoki buni amalga oshirish niyatida, jumladan Curocell, Abclon, GC Cell, Ticaros, Helixmith, Toolgen, Cllengene, Eutilex va Vaxcell Bio.
Koreyada CAR-T davolash klinik sinovini boshlagan birinchi koreys kompaniyasi sifatida Curocell Fevral oyida Oziq-ovqat va dori vositalari xavfsizligi vazirligidan CAR-T davolash nomzodi CRC1 ning 01-bosqich klinik sinovi uchun ruxsat oldi.
The company has used its unique technology known as “overcome immune suppression” to develop CRC01, a CD19 CAR-T therapy that inhibits the expression of immune checkpoint receptors, PD-1 and TIGIT.
Following the recruitment of patients with diffuse large B-cell lymphoma who had relapsed or been refractory after two or more rounds of systemic chemotherapy, the company is currently carrying out the trials at Samsung Medical Centre. The company Curocell, which started the treatment in April, recently stoked anticipation by releasing the preliminary findings of its phase 1 lowest dose cohort data.
At101 CD19 CAR-T terapiyasiga nomzod bo'lib, Abclon iyun oyida 1-bosqich sinovi uchun o'zining yangi dori-darmon arizasini topshirgan edi. Relapsli yoki chidamli B-hujayrali non-Hodgkin limfomasi bo'lgan bemorlar kompaniya uchun maqsadli populyatsiya hisoblanadi.
Regulyatorlar hali korporatsiyaga ruxsat bermagan. GC Cell, Curocell va Abclondan farqli o'laroq, AQShda CAR-T davolashni ishlab chiqmoqchi.
Novacel orqali u mezotelinga xos CAR-T terapiyasi uchun klinik sinov o'tkazmoqchi. Bundan tashqari, kompaniya qattiq saraton bilan shug'ullanmoqchi.
Yirik universitet shifoxonalari CAR-T terapiyasini tadqiq qilishni boshladilar va tegishli infratuzilmalarni yaratishga tayyorlanmoqdalar, shuning uchun CAR-T terapiyalariga qiziqish faqat biznes bilan cheklanmaydi.
Mamlakatdagi birinchi CAR-T hujayralarini davolash qurilmasi aprel oyida Samsung tibbiyot markazida debyut qildi. Seul Muqaddas Meri kasalxonasi va Eutilex sentabr oyida CAR-T terapiyasini ishlab chiqish bo'yicha hamkorlik memorandumini imzoladilar.
Additionally, earlier this month the Ministry of Food and Drug Safety and the Ministry of Health and Welfare gave Seoul National University Hospital their blessing for a clinical trial of CAR-T therapy for paediatric patients with relapsed/refractory acute lymphoblastic leukaemia.
