Türkiye akademik CAR-T hücre (ISIKOK-19) klinik çalışması ön raporu: Ürün karakterizasyonu ve klinik uygulama sonuçları

Objective: 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. Materials and Methods: 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. Results: 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. Conclusion: 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 reseptör T (CAR-T) hücre uygulamaları B-hücreli malignitelerin tedavisinde etkili olmaktadır. CAR-T hücre uygulamalarının sonuçları umut vaadedici olsa da, ticari CAR-T ürünlerinin yükek maliyetleri nedeniyle ulaşılabilirlik açısından ciddi sorunlar yaşanmaktadır. Bu ön raporda, Türkiye’deki ilk akademik CAR-T hücre çalışmasının üretim ve klinik uygulama sonuçları sunulmuştur. Gereç ve Yöntemler: Relaps refrakter CD 19+ hematolojik maligniteli hastalarda ISIKOK-19 T-hücre tedavisinin güvenliği ve etkinliğini değerlendirmek amacıyla yürütülen klinik çalışmaya (NCT04206943) Ekim 2019-Temmuz 2021 tarihleri arasındaki hastalar dahil edilmiştir. Bu raporda ilk 8 hastanın üretim bilgileriyle, ISIKOK-19 hücre infüzyonu yapılan 7 hastanın klinik sonuçları sunulmuştur. Bulgular: Çalışmaya toplam 9 hasta dahil edilmiştir (5 akut lenfoblastik lösemi [ALL] ve 4 non-hodgkin lenfoma [NHL]), ancak sadece 7 hastaya hücre infüzyonu yapılabilmiştir. Hücre infüzyonu alan 3 ALL hastasından 2’sinde ve 4 NHL hastasının 3’ünde tam/kısmi cevap gözlenmiştir (toplam yanıt oranı %72). Dört hastada (%57) CAR-T ilişkili toksisite (sitokin salınım sendromu, immün efektör hücre ilişkili nörotoksisite sendromu ve pansitopeni) tespit edilmiştir. İki hastada ise CAR-T hücre uygulaması sonrası cevapsızlık ve progresif hastalık izlenmiştir. Kısmi cevap veren hastalardan 2’sinde de takip sırasında progresif hastalık tespit edilmiştir. Sonuç: Akademik CAR-T üretimimiz, üretim etkinliği ve kalite kontrol kriterlerinin tam olarak karşılanması açısından tatmin edici sonuçlara sahiptir. Çalışmaya dahil edilen hastaların tedavi yükü hesaba katıldığında tedaviye cevap oranı ve toksisite profili açısından da sonuçlar kabul edilebilir düzeydedir. Bu sonuçlarla, ISIKOK-19 hücrelerinin güvenli, ekonomik ve etkili bir tedavi seçeneği olduğu düşünülebilir. Ancak bu ön sonuçların halen devam eden ISIKOK-19 klinik çalışmasıyla desteklenmesi beklenmektedir

Optimal Sizing and Siting of Different Types of EV Charging Stations in A Real Distribution System Environment

Due to the rising of both economic and environmental concerns in the energy sector, each subdivision of the community is investigating new solutions to overcome this critical issue. For this reason, electric vehicles (EVs) have gained more significance in the transportation sector owing to their efficient and clean operation chance. These improvements, however, bring new challenges such as installation costs, infrastructure renovation, and loading of the existing power system. Here, optimal sizing and siting of EV charging stations (CSs) are examined in a mixed-integer linear programming framework with the aim of minimizing the number of EVCSs in the distribution system (which in turn means to minimize CS-related investment while satisfying EV owners’ needs) while satisfying constraints. The proposed optimization model considers EVCS types with different charging rate capabilities to provide opportunities for demand-side management. Moreover, the model takes the actual behaviour of the battery charging pattern into account by using real measured EV charging data together with the consideration of an actual distribution system belonging to a region in Turkey. Lastly, a bunch of case studies is conducted in order to validate the accuracy and effectiveness of the devised model

Optimal sizing and siting of different types of EV charging stations in a real distribution system environment

Abstract Due to the rising of both economic and environmental concerns in the energy sector, each subdivision of the community is investigating new solutions to overcome this critical issue. For this reason, electric vehicles (EVs) have gained more significance in the transportation sector owing to their efficient and clean operation chance. These improvements, however, bring new challenges such as installation costs, infrastructure renovation, and loading of the existing power system. Here, optimal sizing and siting of EV charging stations (CSs) are examined in a mixed‐integer linear programming framework with the aim of minimizing the number of EVCSs in the distribution system (which in turn means to minimize CS‐related investment while satisfying EV owners' needs) while satisfying constraints. The proposed optimization model considers EVCS types with different charging rate capabilities to provide opportunities for demand‐side management. Moreover, the model takes the actual behaviour of the battery charging pattern into account by using real measured EV charging data together with the consideration of an actual distribution system belonging to a region in Turkey. Lastly, a bunch of case studies is conducted in order to validate the accuracy and effectiveness of the devised model