Hedefleme amacıyla tedavilerde kullanılan geleneksel antikorlar, kanser başta olmak çeşitli hastalıklarda önemli başarılar sağlamıştır. Ancak büyük boyutları ve buna bağlı olarak kısıtlı tümör penetrasyonları, düşük stabiliteleri ve immünojenisiteleri kullanımlarını sınırlandırır. Bu durum zamanla daha küçük antikor fragmanlarına olan ilgiyi artırmıştır. Hamers-Casterman ve ark. şans eseri Camelidae (devegiller) türlerinde ve bazı kıkırdaklı balıklarda (köpek balığı) yeni bir antikor türü keşfetmiştir. Nanoantikor (nanobody) adı verilen bu tam antijen bağlama kapasitesine sahip küçük antikor parçaları, hafif zincirlerden yoksundur. Monoklonal antikorlara nazaran daha küçük boyuta (12-14 kDa) sahip olmaları, yüksek kimyasal ve termal stabiliteleri, suda çözünürlüklerinin yüksek olması, düşük immünojeniklik, kısa kan dolaşım süresine bağlı kandan hızla temizlenme ve yüksek doku penetrasyonu gibi çeşitli avantajları mevcuttur. Ayrıca nanoantikorlar immün, saf ve sentetik kütüphanelerden çeşitli mikroorganizmalar vasıtasıyla, etkin bir şekilde düşük maliyetle ekonomik olarak üretilebilmektedir. Bunun yanında modifikasyona yatkın olmalarından dolayı istenen özelliklere sahip nanoantikorlar araştırmacılar tarafından kolaylıkla tasarlanmaktadır. Nanoantikorlar ilaçlara, toksinlere, radyonüklidlere ve ilaç taşıyıcı sistemlere basitçe konjuge edilebildiğinden bu moleküllerin uygun hedeflere spesifik olarak gönderilmesi için önemli terapötik potansiyel taşımaktadır. Ayrıca kararlı yapıları ve uygulamadan kısa bir süre sonra yüksek tümör-arka planı oluşturmaları nedeniyle tanı ve görüntüleme çalışmalarında sıklıkla kullanılmaktadır. Bu derleme makalesinde nanoantikorların bazı üstün özelliklerinin yanı sıra kanser ve diğer hastalıkların biyomedikal araştırmaları, tanı ve tedavisindeki güncel uygulamalar incelenmiştir.
Anahtar Kelimeler: Nanoantikor; antikor; antineoplastik ajan; moleküler hedefe yönelik tedavi; tanı
Conventional antibodies used in targeting therapies have achieved significant success in various diseases, especially cancer. However, their large size and therefore limited tumor penetration, low stability and immunogenicity limit their use. This has increased interest in smaller antibody fragments over time. By chance, Hamers-Casterman and his team discovered a new type of antibody in Camelidae species and some cartilaginous fish (sharks). These small antibody fragments with full antigen-binding capacity, called nanoantibodies (nanobody), lack light chains. They have various advantages compared to monoclonal antibodies, such as their smaller size (12-14 kDa), high chemical and thermal stability, high water solubility, low immunogenicity, rapid clearance from blood due to short blood circulation time, and high tissue penetration. In addition, nanoantibodies can be produced effectively and economically at low cost from immune, pure and synthetic libraries through various microorganisms. In addition, nanoantibodies with desired properties can be easily designed by researchers because they are prone to modification. Since nanoantibodies can be simply conjugated to drugs, toxins, radionuclides, and drug delivery systems, they have significant therapeutic potential for the specific delivery of these molecules to appropriate targets. In addition, they are frequently used in diagnostic and imaging studies due to their stable structure and high tumor-background formation shortly after application. In this review article, some of the superior properties of nanoantibodies as well as current applications in biomedical research, diagnosis and treatment of cancer and other diseases are examined.
Keywords: Nanobody; antibody; antineoplastic agents; molecular targeted therapy; diagnosis
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