Gastric cancer (GC) takes 5th place among the malignant neoplasms by incidence in the world. Mortality from GC is high, since in most cases the disease is diagnosed in the late stages, with distant metastases, the five-year survival in GC does not exceed 25–30 %. The standard for GC therapy is surgery with chemotherapy. There is a high resistance to chemotherapy in the late stages of GC, and this circumstance requires a fundamentally new therapy. Recently, studies have been actively conducted on the therapy of GC with the immune control point inhibitors. At the moment, the most studied are monoclonal antibodies against PD-1 (Programmed cell death 1, CD279) / PDL1 (Programmed death-ligand 1, CD274), CTLA-4 (Cytotoxic T-lymphocyte-associated protein 4, CD152). The article discusses the characteristics of PD-1, PD-L1, CTLA-4 molecules and their significance in suppressing the T-cell response, as well as the antitumor effect of immune control point inhibitors. The results of clinical studies of GC therapy with monoclonal antibodies against PD-1 / PD-L1, CTLA-4 were analyzed. The immune control point inhibitors are used as both first-line therapy and subsequent ones. The negative side of immunotherapy is immune-mediated adverse events that can affect the tissues of the kidneys, heart, gastrointestinal tract, liver, lungs, skin and endocrine glands. Biomarkers of the effectiveness of the immune control point inhibitors for GC are considered, among which one can distinguish PD-L1 expression, microsatellite instability, gene expression profile, tumor mutational load and composition of the intestinal microbiome.

Carcinoma of the stomach is wide spread malignancy with the poor prognosis. Recent investigations of the genome features let to consider this tumor as heterogeneous lesion, presenting different biological subtypes. Each of those subtypes has its own definitive characteristics including difference in prognosis. Microsatellite instability (MSI) – epigenetic molecular abnormality known in many tumors. The role of MSI in the carcinoma of stomach, prognostic as well predictive, is still not clear. High incidence (10 up to 22 %) of MSI in carcinoma of stomach requires performing more extensive studying of this malignancy. The present review is dedicated to recent data of the literature, concerning clinical, morphological, prognostic and predictive features of MSI in the carcinoma of stomach.

In today’s world, we are constantly exposed to stress. At the same time, if acute stress can have a positive effect on the body, constant stress usually harms health, leading to serious diseases, including cancer, which is considered to be age-related disease. It is also known that stress can significantly deteriorate the efficacy of chemotherapies and anti-tumour immune response, promote tumor growth and metastasis spreading. Meanwhile dopamin known to be antiaging and antistress agent is able to inhibit tumourgenesis. Therefore the role of Central neuronal processes involving the dopaminergic system in the mechanisms of malignant growth control is discussed in the present review.

Bacterial drugs for the treatment of malignant tumors have been discovered more than a hundred years ago, but their use in clinical practice has been very limited. In the past decade, there has been a revival of interest in the development of bacterial-based cancer biotherapies, which is associated with advances in genetic engineering and in depth knowledge of the mechanisms of the infectious process and immunity. The purpose of this review is to examine the current state and prospects for the development and use of drugs based on live bacterium, intended for the treatment of malignant tumors. The review presents evaluation data on experimental models of the antitumor potential of various species and strains of bacteria; the most significant results of clinical trials of bacterial antitumor agents; current trends in the design of bacterial strains for targeted drug delivery to the tumor. It is concluded that development of bacterial drugs for cancer therapy is a perspective branch of experimental oncology.

Retinoic acid (RA) is one of the most functionally active intracellular metabolites of vitamin A, regulating the key physiological processes, including the differentiation of cells, organs and tissues. RA is successfully applied in the treatment of acute promyelocytic leukemia. Drugs based on RA and other natural and synthetic retinoids are being actively developed for the treatment of other oncopathologies, including various solid tumors. However, the use of RA in the treatment of malignant tumors is restricted by the rapid acquisition of RA-resistance. The mechanisms of RA-resistance formation are still poorly understood, what could be explained apparently by the large number of genes directly or indirectly being regulated by RA at transcription level, including genes regulating the activity and metabolism of RA itself. The situation is further complicated by the relatively recently discovered non-genomic or non-canonical activity of RA, which consists in the non-transcriptional regulation of key protein kinases involved in tumor progression. The review is devoted to the analysis of published data on non-canonical activity of RA. The review provides a modern view on the main mechanisms implementing the canonical genomic activity of the RA, presents available information on the RA-dependent non-transcriptional regulation of ERK1 / 2, PI3K / AKT, p38MAPK and PKC protein kinases and possible mechanisms mediating this activity as well as potential significance of the RA-dependent activation of intracellular signaling pathways in the formation of RA-resistance and the malignant potential of transformed cells.

Despite recent advances in targeted and immune therapy, 5‑year overall survival in stages III–IV of melanoma is 50 and 10–20 %, respectively. Modern melanoma biomarkers, which are used in clinical practice, are not sufficiently effective for early diagnosis and prognosis assessment. In the last decade, circulating microRNAs (miRNAs) have come to be regarded as “ideal” melanoma biomarkers. This article presents the characteristics of miRNA biogenesis, as well as provides a critical review of circulating miRNAs as promising diagnostic and prognostic melanoma biomarkers.

Introduction. The main reason for enucleation of the eye when attempting organ-preserving treatment are intraocular tumors that do not respond well to chemotherapy.
Purpose. The aim of the study was to find new effective and safe organ-preserving methods of treatment of intraocular refractory and recurrent retinoblastoma (RB).
Materials and methods. The study included female chinchilla rabbits. The cell line of human RB was intravitreally inserted into the right eye of each animal. The left eye was a control. After obtaining a stable intraocular growth of RB and prolongation of the growth of RB, human cytotoxic lymphocytes (CTL) were intravitreally injected into the affected and control eye K1 at a concentration of 1 × 106 in 0.1 ml suspension and K2 – 5 × 106 in 0.1 ml, respectively.
Results. Histological examination of the removed right eyes in animals confirmed the presence of nodal growth of malignant small-cell tumor on the border of the vascular and retinal membranes (epicenter in the choroid) on the posterior wall of the eye. There was scant lymphoid infiltration, without signs of therapeutic pathomorphosis. In the removed animal»s left eyes there is a preservation of histological structures of the eyeball, without dystrophic changes in the cells of the retina and vascular membranes. In the area of limb unit microcap lymphohistiocytic infiltration (with no elements of the tumor). In the choroid single scattered lymphocytes.
Conclusion. A short period of observation of the tumor did not allow conclusions about the effectiveness of CTL, but the concentrations of CTL used in the experiment did not lead to dystrophic changes in retinal cells and the choroid of the eye, which is an important factor in overcoming the toxicity of the proposed adoptive immunotherapy. At the next stage of the experiment, in our opinion, it is necessary to study in more detail the cytotoxic effect on healthy structures of the eye and the effectiveness of CTL in a larger number of affected rabbit eyes, using their different concentrations and multiplicity of administration. 

Introduction. The increasing clinical use of cellular technologies suggests the possibility of long-term storage of the cellular product while maintaining its viability and basic properties. The procedures of cell’s cryopreservation used in laboratory as well in clinical practice differ a lot. Each method includes two tasks to solve: what is the optimal freezing medium to use and what cryopreservation procedure to prefer. In this paper, we present the method utilized in our center for bone marrow cell cryopreservation. The freezing was carried out in nitrogen vapor after adding the medium containing 95 % dextran [average mw 50 000–70 000] and 5 % dimethylsulfoxid.

Purpose. To show that the proposed method of cryopreservation of dendritic cells is highly effective, simple, reproducible and most convenient for clinical use.

Materials and methods. Viability, expression of surface antigens and stimulating activity towards allogeneic T lymphocytes of cryopreserved mature dendritic cells cultured from peripheral blood monocytes were evaluated.

Results. The first cryopreservation resulted in the death of a small amount of cells. The second freezing procedure increased the proportion of dead cells. Meanwhile, the difference in the expression of the surface antigens in fresh, cryopreserved and re-cryopreserved dendritic cells was not statistically significant. The level of stimulating activity of fresh and cryopreserved dendritic cells did not significantly differ. Conversely the proliferation of allogeneic T lymphocytes was decreased after stimulation with re-cryopreserved dendritic cells.

Conclusion. The presented method of cryopreservation allows to preserve the viability and basic functions of dendritic cells. After thawing dendritic vaccine could be administered to patients after being diluted in an isotonic saline without washing, which makes this method the most convenient for clinical use. 

Introduction. Personalized vaccine therapy that stimulates immune system to recognize mutant tumor neoantigens is one of the promising approaches of cancer treatment.

Objective. Evaluation of immunogenicity and antitumor efficacy of synthetic neoantigen peptides and poly(I:C) adjuvant against murine melanoma B16F10.

Materials and methods. 43 synthetic mutant neoantigen peptides selected earlier according to the bioinformatics analysis of the results of melanoma B16F10 sequencing were investigated. The study was performed in mice C57Bl / 6J with subcutaneously transplanted melanoma B16F10 after double vaccination by peptide groups with or without adjuvant poly(I:C). Immunogenicity of peptides was evaluated by ELISPOT that detected the number of interferon-gamma producing cells. Antitumor activity was evaluated on the base of tumor growth inhibition and the increase of the survival rate.

Results. The number of interferon-gamma producing cells increased after in vitro stimulation by the peptides of the model vaccine in the group of mice which had been vaccinated by these peptides with the adjuvant. The number of interferon-gamma producing cells in vitro did not change after addition of vaccine peptides or any other peptides in the groups of mice that had been vaccinated by the peptides without the adjuvant as compared to the control group. Double vaccination by the peptides with the adjuvant induced a potent antitumor effect in some cases, three of the eight groups of the peptides with the adjuvant induced significant inhibition of tumor growth and the increase of survival rate in mice.

Conclusion. Thereby, it was shown that vaccination of mice by peptides in combination with adjuvant poly(I:C) stimulated the cell immunity response, however, the increase of the number of interferon-gamma producing cells is not an indicator of the antitumor efficacy of neoantigen peptides.

Introduction. Natural killer T lymphocytes (NKT) take place between the innate and acquired immune response. The ability of these cells to activate the antitumor immune response and inhibit immunological activity makes them the target of research in cancer patients. The radicality of surgical treatment of patients with metastatic melanoma (stage III–IV) is relatively conventional. In this regard, the possibility of adjuvant effective therapy of melanoma is actively investigated worldwide.

The aim of the study is investigation of the importance of increasing the number of NKT cells in the peripheral blood of patients with metastatic melanoma after radical surgical removal of the tumor. Patients were treated with adjuvant regimen antitumor autologous dendritic cell therapy in form of vaccination.

Materials and methods. The study included 39 patients with stage III and IV metastatic melanoma with regional and / or distant metastases after radical surgery. From the peripheral blood monocytes of each patient, an autologous vaccine was created from mature dendritic cells loaded with tumor lysate. The therapy continued until objective progression. The study included patients who received from 5 to 120 injections. The follow-up period ranged from 5 to 168 months.

Results. It was shown that 14 (36 %) of patients had the number of NKT cells exceeding the norm (0–10 %) and in the course of vaccine therapy they had the progression of the disease in the period up to 2 years. In patients with relapse-free course of the disease in vaccine therapy (n = 13), the number of NKT lymphocytes did not exceed the norm both before and during therapy. Significantly shorter time to progression was revealed in patients with high initial content of NKT lymphocytes compared with patients with normal indices of NKT cells (6.5 months) – 95 % confidence limit 2,4–10,7 % vs 96,2 months (95 % confidence limit 63.8–128.6 %). 

Conclusion. An increased number of NKT cells in patients with stage III–IV metastatic melanoma after radical surgical treatment is a marker of early progression.