Delivery systems of STING agonists for the immunotherapy of malignant neoplasms

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Abstract

Background. One of the key components of innate immune signaling pathways, the STING (STimulator of INterferon Genes) protein, is currently a promising target for cancer immunotherapy. Activation of STING leads to the production of inflammatory cytokines, in particular type 1 interferons, which provide an antitumor immune response. The clinical potential of STING agonists is limited by their systemic toxicity due to their relatively non-specific action. One of the approaches to expand the therapeutic index of drugs is to modify the native structure of STING agonists to make them more sensitive to physiologically relevant stimuli. Another approach is to develop efficient delivery system that reduce the impact of encapsulated STING agonists on healthy tissues.

Aim. Systematization and generalization the literature data on the development of delivery systems of STING agonists based on immunoconjugates, liposomes, and polymer nanoparticles.

Results. The delivery systems discussed show significant potential for enhancing the efficacy of STING agonist-based immunotherapy for malignant neoplasms. As substances exhibiting therapeutically relevant activity in the nanomolar concentration range, STING agonists represent a suitable candidate as a payload of immunoconjugates. During the pharmaceutical development of such a delivery system, it is necessary to take into account the properties of its structural components, primarily the STING agonist itself. The result is almost always a unique product: a molecular construct capable of selectively delivering the STING activator to the tumor microenvironment while minimizing systemic side effects. Encapsulation of STING agonists, particularly cyclic dinucleotides, within nanoparticles serves as an effective tool for increasing their in vivo stability, improving cellular uptake, and reducing systemic toxicity.

Conclusion. The development of innovative delivery systems is a critical factor for the successful clinical implementation of STING agonist-based biotherapy for malignant neoplasms. The flexibility of the structure of nanoplatforms allows for their further modification and optimization, including the improvements in manufacturing technology to obtain a stable product with specified characteristics.

About the authors

Stepan D. Shceglov

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia; Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)

Author for correspondence.
Email: stepanshceglov@mail.ru
ORCID iD: 0009-0002-0777-0422
Russian Federation, 24 Kashirskoe Shosse, Moscow 115522; Build. 2, 8 Trubetskaya St., Moscow 119048

Yana O. Sadovskaya

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: stepanshceglov@mail.ru
ORCID iD: 0009-0009-7115-7797
Russian Federation, 24 Kashirskoe Shosse, Moscow 115522

Anastasia O. Karimova

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia; National Research University Higher School of Economics

Email: stepanshceglov@mail.ru
ORCID iD: 0009-0000-0317-9948
Russian Federation, 24 Kashirskoe Shosse, Moscow 115522; 20 Myasnitskaya St., Moscow 101000

Olga N. Solopova

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: stepanshceglov@mail.ru
ORCID iD: 0000-0002-5465-6094
Russian Federation, 24 Kashirskoe Shosse, Moscow 115522

Zhanna M. Kozlova

Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)

Email: aganusya1@yandex.ru
ORCID iD: 0000-0003-1525-732X
Russian Federation, Build. 2, 8 Trubetskaya St., Moscow 119048

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