Published January 21, 2021 | Version v1
Journal article Open

mRNA Based Therapeutic Strategies in Cancer Immunotherapy

Creators

  • 1. Department of Pediatrics, Gulhane Medical Faculty, University of Health Sciences, Ankara, Turkey

Description

Özet

Haberci RNA (messenger RNA, mRNA), mikroRNA ve küçük engelleyici RNA (small interfering RNA, siRNA) temelli terapötik yaklaşımlar fizyolojik veya patolojik süreçlere hücresel düzeyde müdahaleyi mümkün kılan yeni bir tedavi sınıfıdır. RNA temelli teknolojinin kullanıldığı bir siRNA sisteminin 2018 yılında kullanım onayı almasından kısa bir süre sonra patlak veren SARS-CoV-2 pandemisinde çok sayıda mRNA temelli aşı platformunun klinik öncesi ve klinik çalışma aşamalarına gelmesi ve 2020 Aralık ayı içerisinde iki farklı mRNA aşısının birçok gelişmiş ülkede acil kullanım onayları alması bu yeni teknolojinin önündeki en büyük engellerden biri olan güvenlik kaygılarını önemli ölçüde ortadan kaldırmıştır. Enfeksiyöz etkenlere karşı geliştirilen aşılardan farklı olarak, kanser immünoterapisi “mRNA temelli aşılama prensibi ile otolog dentritik hücrelerin kullanıldığı hücresel tedavi yaklaşımının” kombine edilmesini içerir. Antikanser mRNA aşıları olarak da adlandırılan bu sistem bilinen aşı yaklaşımlarının temel hedefi olan bağışıklık sistemini uyarma ve aktive etme prensibi yanında bazı genlerin baskılanması gibi farklı terapötik amaçları da içeren daha karmaşık bir tedavi yaklaşımıdır. Bu teknolojinin başta malign melanom ve glioblastoma olmak üzere çeşitli kanserlere yönelik tedavi amaçlı kullanımının yaygınlaşmasında “immün sistemin temel fonksiyonların gün geçtikçe daha iyi anlaşılması, yüksek kapasiteli dizi analizi sistemleri gibi moleküler biyolojideki teknik ilerlemeler ve genetik mühendisliği alanındaki yeni gelişmelerin” önemli katkıları olmuştur. Bu makalede mRNA temelli kanser immünoterapisinin temel prensipleri ele alınmış ve kişiselleştirilmiş kanser immünoterapisi gibi bu alandaki yeni gelişmelere değinilmiştir.

Abstract

Therapeutic approaches based on messenger RNA (messenger RNA, mRNA), microRNA and small interfering RNA (siRNA) are a new class of therapies that enable intervention in physiological or pathological processes at the cellular level. In the SARS-CoV-2 pandemic, which broke out shortly after an siRNA system using RNA-based technology was approved for clinical use in 2018, numerous mRNA-based vaccine platforms reached in pre-clinical and clinical trial stages and in December 2020, two different mRNA vaccines were approved for emergency use in many developed countries. Thus, safety concerns, which are one of the biggest obstacles to this new technology, have been removed to a great extent. Unlike vaccines developed against infectious agents, cancer immunotherapy involves the combination of "mRNA-based vaccination principle and cellular therapy approach using autologous dendritic cells". This system, also called anticancer mRNA vaccines, is a more complex treatment approach that includes different therapeutic purposes such as suppression of some genes as well as the principle of stimulating and activating the immune system, which is the main target of known vaccine approaches. “Better understanding of the basic functions of the immune system, technical advances in molecular biology such as high-capacity sequence analysis systems and new developments in the field of genetic engineering” have contributed significantly to the widespread use of this technology for therapeutic purposes for various cancers, especially malignant melanoma and glioblastoma. In this article, basic principles of mRNA-based cancer immunotherapy are discussed and new developments in this field such as personalized cancer immunotherapy are mentioned.

Notes

Kanser İmmünoterapisinde mRNA Temelli Terapötik Stratejiler

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