Journal of Literature Pharmacy Sciences

Güncel Tedavi Yaklaşımlarından Olan Antikor İlaç Konjugatlarında Amatoksin Konjugatlarının Kullanımı: Sistematik Derleme
Use of Amatoxin Conjugates in Antibody Drug Conjugates, One of the Current Treatment Approaches: Systematic Review
Hande YÜCEa, Songül ÜNÜVARa
aİnönü Üniversitesi Eczacılık Fakültesi, Farmasötik Toksikoloji ABD, Malatya, Türkiye
J Lit Pharm Sci. 2022;11(2):170-6
doi: 10.5336/pharmsci.2021-86316
Article Language: TR
Full Text
ÖZET
Geleneksel kanser kemoterapisinde kullanılan ajanlar düşük terapötik indekse sahiptirler. Bu nedenle monoklonal bir antikor, bağlayıcı bir molekül ve sitotoksik bir ajandan oluşan immünokonjugatlar olan antikor-ilaç konjugatları (AİK) geliştirilmiştir. Tümör hücrelerinde bulunan çeşitli hedef moleküllere yönelik geliştirilmiş olan bu konjugatlar, son yıllarda kanser tedavisinde kullanılmaya başlanmıştır. Kemoterapide uygulanan geleneksel tedavi yöntemlerine kıyasla bu ajanlar, yüksek düzeyde seçiciliğe ve düşük yan etki profiline sahiptirler. Bu özellikleri, standart tedaviler içinde yer almalarını sağlamıştır. Yeni geliştirilen bu konjugatlar ile ilacın doğrudan kanser hücreleri üzerine hedeflenmesi amaçlanmaktadır. Buna bağlı olarak da sistemik toksisitenin azaltılması ve tedavi etkinliğinin artırılması hedeflenmektedir. Son yıllarda farklı sitotoksik ajanlar AİK'lerinde kullanılmışlardır. Sitotoksik ajanlar; tübülin hasarı yapanlar ve DNA hasarı yapanlar olmak üzere 2 ayrı mekanizmaya sahiptirler. Amanitin bazlı AİK'leri ise RNA polimeraz II üzerinde inhibitör etki göstermektedirler. Bu şekilde çok düşük konsantrasyonlarda bile DNA transkripsiyonunu inhibe etmektedirler. Bu konjugatlar, tümör mikro-ortamı ile dinamik etkileşime girerek, terapötik etkinlikte artış sağlarlar. Amanitin bazlı konjugatların geliştirilmesi oldukça yeni bir yaklaşımdır. Amanitin, çoklu ilaç direnci gösteren tümör hücreleri üzerinde düşük konsantrasyonlarda bile yüksek sitotoksik etki gösterir. AİK'lerinin tasarlanması, bireyselleştirilmiş kanser tedavilerinin geliştirilmesine önemli katkı sağlayacaktır. Son yıllarda amanitin toksini, AİK'lerinin yapısında yer alan ajanlardan biridir. Mikrogram düzeylerde bile pek çok tümörün mikro çevresinde sitotoksik etki gösterir. Bu derlemede amatoksin konjugatları ile ilgili güncel bilgilere yer verilmiştir.

Anahtar Kelimeler: Amatoksin; antikor-ilaç konjugatları; kemoterapi; monoklonal antikorlar
ABSTRACT
Agents used in conventional cancer chemotherapy have a low therapeutic index. Therefore, antibody-drug conjugates (ADCs), which are immunoconjugates composed of a monoclonal antibody, a binding molecule, and a cytotoxic agent, have been developed. These conjugates, which have been developed for various target molecules in tumor cells, have been used in cancer treatment in recent years. Compared to conventional treatment methods used in chemotherapy, these agents have high selectivity and a low side-effect profile. These features have enabled them to be included in standard treatments. With these newly developed conjugates, it is aimed to target the drug directly on cancer cells. Accordingly, it is aimed to reduce systemic toxicity and increase treatment efficiency. In recent years, different cytotoxic agents have been used in ADCs. Cytotoxic agents; have two separate mechanisms: those that cause tubulin damage and those that do DNA damage. Amanitin-based ADCs show an inhibitory effect on RNA polymerase II. In this way, they inhibit DNA transcription even at very low concentrations. These conjugates interact dynamically with the tumor microenvironment, resulting in increased therapeutic efficacy. The development of amanitin-based conjugates is a fairly new approach. Amanitin exerts a high cytotoxic effect on multidrug resistant tumor cells even at low concentrations. Designing ADCs will make a significant contribution to the development of individualized cancer treatments. In recent years, amanitin toxin is one of the agents involved in the structure of ADCs. Even at microgram levels, it has a cytotoxic effect in the microenvironment of many tumors. In this review, up-to-date information about amatoxin conjugates is given.

Keywords: Amatoxin; antibody-drug conjugates; chemotherapy; monoclonal antibodies
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Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. may block the website to users in the following events:

-Information with wrong, incomplete, deceiving or immoral expressions is recorded to the website,

-Proclamation, advertisement, announcement, libelous expressions are used against natural person or legal identity,

-During various attacks to the website,

-Disruption of the website because of a virus.

Written, visual and audible materials of the website, including the code and the software are under protection by legal legislation.

Without the written consent of Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. the information on the website cannot be downloaded, changed, reproduced, copied, republished, posted or distributed.

All rights of the software and the design of the website belong to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. will be pleased to hear your comments about our terms of use. Please share the subjects you think may enrich our website or if there is any problem regarding our website.

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