Personalized neoantigen vaccines are a group of individually designed cancer vaccines that enhance patients’ own antigen-specific immune responses. These include vaccines based on dendritic cells, DNA, mRNA and synthetic peptides. An analysis of 98 clinical trials of neoantigenic vaccines from the ClinicalTrials.gov database found that peptide vaccines are one of the most popular cancer vaccines, accounting for about 50 % of clinical trials. They usually consist of a mixture of long or short peptides, dissolved depending on their properties in an appropriate solvent, and an adjuvant that stabilizes and increases their effectiveness. The most used immunoadjuvants in the formulation of neopeptide vaccines are Toll-like receptor agonists (poly-ICLC) and granulocyte-macrophage colony-stimulating factor. The development of neoantigenic vaccines presents a number of distinctive challenges compared to other types of vaccines. The process should cover and validate the various steps in the development, production and administration processes in order to maximize the efficacy and safety of vaccines. In the technology for the production of peptide vaccines, 3 main stages can be distinguished: 1) screening and identification of neoepitopes using the approaches of computer prediction, co-immunoprecipitation, mass spectrometry and cytotoxic experiments; 2) synthesis of peptides by methods of standard solid-phase synthetic peptide chemistry; 3) actually obtaining a vaccine preparation suitable for storage, transportation and administration to the patient. Taking into account the specificity of the drug, the manufacturing process must be carried out strictly according to the Good Manufacturing Practice standard with mandatory quality control of intermediate and finished products

Antitumor vaccines are aimed at correcting cellular immunity by overcoming immunological tolerance with eluding surveillance due to the specific presentation of tumor-associated or tumor-specific antigens to immunocompetent cells.
The purpose of this review was to study modern strategies for the development of antitumor vaccines containing epitopes of HER2/neu receptors acting as tumor-associated antigens. Approaches to the creation of such vaccines are classified by targeting the T-cell link or B-cells by the choice and length of the epitopes used or by the use of specific adjuvants.
The review provides information on this topic, obtained from more than 50 publications of the last 20 years, found in the most significant sources of citation. The text is categorized for the convenience of perception by scientists of different specialties and is completed with a brief conclusion with an emphasis on development prospects. The results of clinical studies of vaccines with an analysis of the immunological features of the results of immunotherapy, mainly breast cancer with HER2/neu expression, are considered. Vaccines targeting different histocompatibility complexes are compared. The review traces the evolution of vaccine preparations from the simplest containing short peptide sequences to complex combined systems, including viral vectors. Attention is paid to various methodological approaches used in the development of such drugs: from computer design and phage display in experiments in vitro/in vivo. The emphasis is placed on the problem of a personalized approach to vaccination of an oncological patient associated with a mutation process occurring inside tumors and leading to the appearance of unique tumor-associated antigens. The participation of complement system components in antibody-mediated lysis of tumor cells induced by the presented vaccines is discussed.
Thus, the review introduces readers to the existing directions of creating immune drugs designed to suppress the development of the tumor process by activating the body’s own immune forces and the prospect of their development.

Background. Interferons are the most important component of nonspecific (congenital) resistance of the body, the history of their discovery dates back to 1957 and the study is still ongoing. Evaluation of an individual interferon status (IS) with the estimation of the sensitivity of leukocytes to immune reactive drugs has a practical aspect. IS is a set of parameters indicating the state of nonspecific resistance.
Aim. To study the problems of standardizing the IS tests with the search for possible ways of standardizing the method and calculate reference values based on a large amount of data.
Materials and methods. A retrospective statistical processing was performed using the database of the IS tests performed in the clinical diagnostic department of the laboratory center of Exacte Labs LLC from September 2020 to August 2022. Enzyme immunoassay kits based on commercial reagents were used. The paper describes the methodology for studying IS with an emphasis on the least standardized procedures.
Results. Reference values were calculated using three indirect methods. The analysis of the results obtained made it possible to identify age groups for which it is advisable to establish reference values. The study results showed the inconsistency of the obtained reference values as compared with the previous ones, which indicates the need for their correction.
Conclusion. The considered problems of performing and standardizing the method for IS analysis are of practical importance for establishing a standard methodology and an in vitro method. The reference values have been updated to avoid errors in the interpretation of the results and to increase the clinical significance of the study.

Aim. The screening of molecular genetic markers for a minimally invasive assessment of the radiation therapy effectiveness for rectum malignant tumors.

Materials and methods. The study was carried out in 4 stages: 1) bioinformatic analysis of TCGA (The Cancer Ge- nome Atlas) databases using the GISTIC algorithm; 2) validation of bioinformatics analysis data in a model experiment on cell culture; 3) study of genes copy number features validated in a model experiment in patients with different responses to radiation therapy; 4) determination of the gene copy number in cell-free DNA in patientswith different responses to radiation therapy. 100 patients with rectum adenocarcinoma (G1–2), as well as 30 apparently healthy individuals, took part in the work. Radiotherapy was carried out according to the standard protocol (single focal dose 2.4 Gy, total focal dose 54 Gy) on a Novalis TX linear accelerator. The relative copy number of genetic loci was determined by real-time quantitative polymerase chain reaction.

Results. Bioinformatic analysis revealed 32 candidate genetic loci. Validation of these markers on irradiated HT-29 cells showed that the copy number of BRCA2, H2AX, CASP9 and RBBP8 genes was increased, while the copy number of BCL2 gene was reduced relative to intact cells. In 74 patients with a partial response to radiation therapy, an increase in the copy number of BRCA2, H2AX, RBBP8 and BCL2 was found, which positively correlated with the copy number of these genes in blood plasma cell-free DNA.

Conclusion. The application of an integrated approach based on TCGA database bioinformatic analysis, radiation therapy modeling in cell culture and validation of the identified markers on tissue and blood samples of patients with rectal adenocarcinoma revealed RBBP8, BRCA2, H2AX and BCL2 genes copy number association with the preoperative radiation therapy effectiveness.

Background. Immunotropic drugs are widely used in the modern strategy of cancer treatment. Importance is given to immunological markers of the tumor, which determine the prognosis of the disease, the effectiveness of treatment. Therefore, the study of their expression is one of the leading scientific directions. Of particular interest is the study of monomorphic HLA determinants, transferrin receptor 1 (TfR1), depending on its biological subtype of breast cancer.

Aim. To evaluate the frequency of expression of HLA class I, II, TfR1 molecules by breast cancer cells and determine their relationship with the molecular biological subtype of the tumor.

Materials and methods. This study included 120 patients with breast cancer who received treatment at the N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia. Tumor stages II and III prevailed: 56.7 % and 33.4 %, respectively. A moderate degree of differentiation (G₂) was more often noted. The luminal subtype was 58.3 % (n = 70), non-luminal – in 41.7 % (n = 50). Immunophenotyping of the primary tumor was performed by immunofluorescence on cryostat sections. The reaction was evaluated using a ZEISS Axioscope 5 luminescent microscope (Zeiss AG, Germany). The frequency of expression of HLA class I and II molecules were studied depending on the clinical and morphological characteristics of breast cancer. The frequency of expression of HLA class I, HLA-DR, TfR1, molecules, toumor infiltration of СD45+, CD38+, depending on the molecular subtype of breast cancer was studied.

Results. It was found that the frequency of expression of monomorphic determinants of the HLA class I in luminal and non-luminal subtypes of breast cancer was comparable; HLA-DR was expressed significantly more often in the luminal subtype of breast cancer: 37.3 % and 18.0 %, respectively, p = 0.022. The frequency of TfR1 expression was significantly higher in the luminal subtype of cancer compared to non-luminal, p = 0.014. Predominantly monomorphic type of reaction was observed: in 76.5 % (n = 39) of cases. The mosaic type of the TfR1 reaction was noted in 7.8 % of the samples. TfR1 monomorphic expression was detected in 50.0 % (n = 30) of cases in non-luminal cancer, the mosaic expression – in 20.0 % (n = 12) of cases. A pronounced degree of lymphoid infiltration, in particular plasmacytic, was established in non-luminal subtype of breast cancer: 70.7 % (n = 29) and 35.0 % (n = 14), respectively, p = 0.001. An association was noted between the expression of HLA I class molecules and the severity of general leukocyte infiltration, p = 0.007.

Conclusion. The frequency of expression of HLA class I monomorphic determinants did not differ in molecular subtypes of breast cancer. The expression of the HLA class II molecule was significantly more frequently observed in the luminal subtype of breast cancer. The expression of HLA class I monomorphic determinants is associated with the degree of lymphoid infiltration of the tumor. In the non-luminal subtype, plasmacytic infiltration is more pronounced. The expression of transferrin receptors is significantly more pronounced in the luminal subtype.

Background. Enzyme prodrug therapy is a promising strategy to treat solid malignancies. The utilization of two-component systems, including an enzyme and a non-toxic prodrug, to generate cytotoxic compounds directly at the surface of the tumor cell can be successful strategy in reducing the overall toxic load on the body.

Aim. To determine antitumor activity of the pharmacological pair C115H methionine γ-lyase (C115H MGL) conjugated with daidzein (C115H MGL-Dz) and of S-alk(en)yl-L-cysteine sulfoxides against various types of solid tumors in vitro and in vivo.

Materials. MTT-test was used to determine the cytotoxicity of C115H MGL-Dz in the presence of S-alk(en)yl-L-cysteine sulfoxides in vitro against Sw620 (colon cancer), Panc1 (pancreatic cancer), and 22Rv1 (prostate cancer). Apopto- sis induction and cell cycle alteration in 22Rv1, Sw620, and SKBR3 cell lines were studied using the Muse® Caspase-3/7 and Muse® Cell Cycle Assay kits. In vivo anticancer activity was studied on Sw620, Panc1, and 22Rv1 subcutaneous xenografts in Balb/c nude mice.

Results. The C115H MGL-Dz had the maximum cytotoxic activity in the presence of S-propyl-L-cysteine sulfoxide (propiin) with IC₅₀ values: 3.88 and 5.4 for Panc1 and 22Rv1, respectively. Dipropyl thiosulfinate formed by the β-eli-mination of propiin catalyzed by C115H MGL-Dz, induces apoptosis through both the activation of caspases and alternative pathways, and also it inhibits cell division, contributing to a decrease in the concentration of cells in the G₂/M phase. The anticancer efficacy of the pharmacological pair C115H-Dz/propiin in vivo indicated a significant decrease in Panc1 tumor volume (tumor growth inhibition (TGI) 67.5 %, p = 0.004), Sw620 (TGI 22.07 %, p = 0.12) and 22Rv1 (TGI 70 %, p = 0.043).

Conclusion. Pharmacological pair C115H MGL-Dz/propiin was capable of suppressing tumor development in malignant solid tumors and might be considered as a potential anticancer approach in cancer prodrug therapy.

Background. The development of a pneumococcal vaccine with serotype-independent activity is relevant for the whole world, as this is due to the high prevalence of Streptococcus pneumoniae (S. pneumoniae), the constant change of pathogen serotypes and the growth of antibiotic-resistant strains. In previous experiments, we revealed a protective effect of immunization with recombinant pneumolysin (rPly) in a model of systemic infection caused by S. pneumoniae serotype 3.

Aim. Study of serotype-independent protective activity of rPly.

Materials and methods. Strains of S. pneumoniae serotypes 4 and 6B were used. Mice were immunized intraperi-toneally two or three times with an interval of 14 days with rPly. To assess the protective activity of rPly, animals after double or triple immunization were infected intraperitoneally with S. pneumoniae .

Results. rPly at a triple immunization in a dose of 25 μg protected mice from intraperitoneal infection with S. pneu- moniae serotype 4, the efficiency index increased by 2 times compared with the control. with a double immunization, rPly protected mice from intraperitoneal infection with S. pneumoniae serotype 6B, efficiency index increased by 6.61 times compared with the control.

Conclusion. rPly protects animals from infection with different serotypes of S. pneumoniae, which allows us to consider it a promising drug for the development of pneumococcal vaccines with serotype-independent activity.

Background. The new anticancer chemical compound LHS-1269 from the class of indolocarbazoles is undergoing preclinical studies at the N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia. LHS-1269 has a high antitumor activity on transplanted tumors of mice, showed high cytotoxic activity on many tumor cells lines in vitro, and has shown an inhibitory effect on vasculogenic mimicry in tumors in vitro. LHS-1269 does not affect the catalytic activity of human topoisomerases I and IIα. An antiangiogenic mechanism of the drug’s antitumor action is suggested.

Aim. To evaluate the effect of LHS-1269 on the morphological features and angiogenesis of transplanted Lewis lung carcinoma (LLC) in BDF₁ mice.

Materials and methods. In BDF₁ mice (n = 20) with transplanted LLC tumor on days 1 and 3 after 5-fold intraperitoneal administration of LHS-1269 in a single dose of 60 mg (total dose – 300 mg/kg), mice (n = 20) on days 5 and 8 after a single intravenous injection of LHS-1269 at a dose of 100 mg/kg, mice (n = 20) with transplanted LLC tumor without administration of LHS-1269 (control). The assessment of the antitumor effect was carried out according to the criterion of inhibition of tumor growth (%) and the study of the morphological features of the tumors. To assess the effect of LHS-1269 on tumor angiogenesis in LLC tumor sections, a visual calculation of the average number (density) of blood vessels and immunohistochemical detection of expression of the CD31+ endothelial marker were performed.

Results. The LHS-1269 compound in animal groups with 5-fold and 1-fold use caused tumor growth inhibition – 59–70 and 67–79 %, with pronounced morphological changes and tumor cell death. There is an uneven distribution of blood vessels in tumors and surrounding tissues in all groups. LHS-1269 caused a statistically significant decrease in the average number of blood vessels in the tumor both after 5-fold and after 1-fold administration. The statistically significant decrease in the average number of blood vessels in the surrounding connective tissue tumor was observed only after 5-fold administration of the drug. The decrease in the average number of CD31+ endothelial cells after five times intraperitoneal administration was statistically insignificant compared to control (83.1 ± 8.7 and 59.6 ± 18.9, respectively). The increase in this indicator after a single intravenous injection of LHS-1269 was statistically significant.

Conclusion. LHS-1269, when administered five times and once in mice, caused pronounced morphological changes in the form of damage and death of LLC tumor cells. The results of a study of angiogenesis in a tumor do not allow an unambiguous conclusion about the inhibitory effect of LHS-1269 on angiogenesis in LLC tumors in mice.