Cancer vaccine adjuvants

В обзоре рассмотрены и проанализированы данные литературы о функциях семейства толл-подобных рецепторов (ТПР), значимых для опухолевого процесса, кратко отражены такие важные аспекты, как строение ТПР, механизмы внутриклеточной передачи сигнала, известные специфические лиганды и агонисты ТПР. Кроме того, описаны эффекты воздействия на различные ТПР с точки зрения влияния на рост самой опухоли и реакций клеточного иммунитета. Приведено сравнение неоднозначных результатов экспериментального изучения и клинического применения агонистов и антагонистов ТПР. Сделан вывод о необходимости получения информации об отсутствии стимуляции опухолевого роста in vivo агонистов ТПР на этапе доклинического изучения.

Section: заключениеunclassified

The different roles of toll-like receptors in oncotherapy

Трещалина

Михайлова

Киселевский

2019

Comparison of Ridostin Pro and Poly(I:C) as adjuvant for a cancer neoantigen peptide vaccine

Барышникова

Пономарев

Рудакова

et al. 2022

Self Cite

Background. The effectiveness of cancer neoantigen peptide vaccines depends on the presence of an adjuvant in their composition. Poly(I:C), a TRL-3 agonist, is used as an adjuvant in mouse models of cancer vaccines, but has limitations for use in humans. Therefore, the search for new effective adjuvants for inclusion in the composition of cancer neoantigen peptide vaccine is relevant. Ridostin Pro is a domestic drug that contains a natural complex of sodium salts of double-chiral and single-chiral ribonucleic acids, is an agonist of TLR-3, an inducer of interferon, its antiviral activity is shown. In this regard, the study of Ridostin Pro as an adjuvant in the composition of neoantigen peptide vaccines is of interest.Aim. To evaluate the ability of Ridostin Pro and Poly(I:C) adjuvants enhance the specific T-cell response to neoantigen synthetic peptides; to study the antitumor efficacy of a neoantigen peptide vaccine with Ridostin Pro or Poly(I:C) adjuvants.Materials and methods. Immunogenicity of peptides after vaccination with Ridostin Pro or Poly(I:C) adjuvants evaluated with ELISpot. Antitumor effect of Ridostin Pro or Poly(I:C) adjuvants were evaluated on a mouse model of the B16-F10 tumor by the effect on the tumor growth rate and survival of mice.Results. Vaccination of mice with Ridostin Pro or Poly(I:C) with neoantigen peptides contributed to the appearance of a specific immune response to peptides that were part of the vaccine. Ridostin Pro, both as part of a vaccine model and when administered without a peptide, inhibits tumor growth and increases the life expectancy of mice with melanoma B16-F10.Conclusion. Ridostin Pro promotes the formation of a specific immune response to the peptide vaccine, enhances the antitumor effect of the vaccine. These results confirm that Ridostin Pro may prove to be an effective adjuvant for personalized neoantigen peptide vaccines.

Study of Ridostin Pro and Poly(I:C) as adjuvants for cancer vaccine on the E.G7-OVA model

Tsarapaev,

Baryshnikova,

Ponomarev

et al. 2024

Background. Adjuvant is necessary for enhancing the efficacy of cancer peptide vaccines. Our previous work has demonstrated the efficacy of TRL-3 agonists, which include Poly(I:C) and Ridostin Pro, as part of peptide neoantigen vaccines against murine melanoma B16-F10.Aim. To evaluate the antitumor efficacy of Ridostin Pro or Poly(I:C) against murine lymphoma E.G7-OVA.Materials and methods. The study was performed on C57Bl / 6 mice with subcutaneously transplanted E.G7-OVA lymphoma containing the complete chicken ovalbumin sequence. The antitumor effects of Ridostin Pro and Poly(I:C) were evaluated in monotherapy as well as in vaccines containing chicken ovalbumin in addition to the adjuvant. The antitumor effect of Ridostin Pro and Poly(I:C) was evaluated when used in different vaccination regimens: in one case treatment was started after tumour transplantation and in the other case before tumour transplantation. The criteria of antitumor response were inhibition of tumour growth, increased survival of mice and cure.Results. Ridostin Pro and Poly(I:C) both as part of the vaccine and when administered without ovalbumin increased the percentage of tumour growth inhibition and survival of mice with E.G7-OVA lymphoma. In a regime where vaccination with ovalbumin and Ridostin Pro or Poly(I:C) was started before tumour transfection, a complete cure of the mice was shown.Conclusion. Ridostin Pro and Poly(I:C) enhance the antitumor effect of a peptide vaccine against E.G7-OVA lymphoma.