土耳其学术型 CAR-T (ISIKOK-19) 细胞临床试验初步报告：产品表征与临床应用结局

Chimeric antigen receptor T (CAR-T) cell therapies have already made an impact on the treatment of B-cell malignancies. Although CAR-T cell therapies are promising, there are concerns about commercial products regarding their affordability and sustainability. In this preliminary study, the results of the first production and clinical data of an academic CAR-T cell (ISIKOK-19) trial in Turkey are presented.

A pilot clinical trial (NCT04206943) designed to assess the safety and feasibility of ISIKOK-19 T-cell therapy for patients with relapsed and refractory CD19+ tumors was conducted and participating patients received ISIKOK-19 infusions between October 2019 and July 2021. The production data of the first 8 patients and the clinical outcome of 7 patients who received ISIKOK-19 cell infusions are presented in this study.

Nine patients were enrolled in the trial [5 with acute lymphoblastic leukemia (ALL) and 4 with non-Hodgkin lymphoma (NHL)], but only 7 patients could receive treatment. Two of the 3 participating ALL patients and 3 of the 4 NHL patients had complete/partial response (overall response rate: 72%). Four patients (57%) had CAR-T-related toxicities (cytokine release syndrome, CAR-T-related encephalopathy syndrome, and pancytopenia). Two patients were unresponsive and had progressive disease following CAR-T therapy. Two patients with partial response had progressive disease during follow-up.

Production efficacy and fulfillment of the criteria of quality control were satisfactory for academic production. Response rates and toxicity profiles were also acceptable for this heavily pretreated/refractory patient group. ISIKOK-19 cells appear to be a safe, economical, and efficient treatment option for CD19+ tumors. However, the findings of this study need to be supported by the currently ongoing ISIKOK-19 clinical trial. AMAÇ: Kimerik antijen resept r T (CAR-T) h cre uygulamalar B-h creli malignitelerin tedavisinde etkili olmaktad r. CAR-T h cre uygulamalar n n sonu lar umut vaadedici olsa da, ticari CAR-T r nlerinin y kek maliyetleri nedeniyle ula labilirlik a s ndan ciddi sorunlar ya anmaktad r. Bu n raporda, T rkiye deki ilk akademik CAR-T h cre al mas n n retim ve klinik uygulama sonu lar sunulmu tur. GEREÇ VE YÖNTEMLER: Relaps refrakter CD 19+ hematolojik maligniteli hastalarda ISIKOK-19 T-h cre tedavisinin g venli i ve etkinli ini de erlendirmek amac yla y r t len klinik al maya (NCT04206943) Ekim 2019-Temmuz 2021 tarihleri aras ndaki hastalar dahil edilmi tir. Bu raporda ilk 8 hastan n retim bilgileriyle, ISIKOK-19 h cre inf zyonu yap lan 7 hastan n klinik sonu lar sunulmu tur. BULGULAR: al maya toplam 9 hasta dahil edilmi tir (5 akut lenfoblastik l semi [ALL] ve 4 non-hodgkin lenfoma [NHL]), ancak sadece 7 hastaya h cre inf zyonu yap labilmi tir. H cre inf zyonu alan 3 ALL hastas ndan 2 sinde ve 4 NHL hastas n n 3 nde tam/k smi cevap g zlenmi tir (toplam yan t oran %72). D rt hastada (%57) CAR-T ili kili toksisite (sitokin sal n m sendromu, imm n efekt r h cre ili kili n rotoksisite sendromu ve pansitopeni) tespit edilmi tir. ki hastada ise CAR-T h cre uygulamas sonras cevaps zl k ve progresif hastal k izlenmi tir. K smi cevap veren hastalardan 2 sinde de takip s ras nda progresif hastal k tespit edilmi tir. SONUÇ: Akademik CAR-T retimimiz, retim etkinli i ve kalite kontrol kriterlerinin tam olarak kar lanmas a s ndan tatmin edici sonu lara sahiptir. al maya dahil edilen hastalar n tedavi y k hesaba kat ld nda tedaviye cevap oran ve toksisite profili a s ndan da sonu lar kabul edilebilir d zeydedir. Bu sonu larla, ISIKOK-19 h crelerinin g venli, ekonomik ve etkili bir tedavi se ene i oldu u d n lebilir. Ancak bu n sonu lar n halen devam eden ISIKOK-19 klinik al mas yla desteklenmesi beklenmektedir.