Use of xenogeneic vaccine modified with embryonal nervous tissue antigens in the treatment of B16-melanoma-bearing mice.

UNLABELLED: The aim of the work was experimental study of anticancer efficacy of xenogeneic cancer vaccine (XCV) developed on the basis of rat embryonic nervous tissue and protein-containing metabolite of Bacillus subtilis В-7015 (70 kDa), in В-16 melanoma-bearing С57Bl/6 mice. METHODS: Immunological methods and methods of experimental oncology were used. Effects of XCV on primary and secondary organs of immune system of experimental animals, its anticancer and antimetastatic efficacy were evaluated. RESULTS: It has been shown that XCV did not induced toxic effects on organism, and did not caused inflammatory reactions. The relation between the degree of XCV anticancer efficacy with the regimen of its use and the presence of primary tumor has been analyzed. It has been demonstrated that the developed XCV possesses significant antimetastatic activity if it is used after surgical removal of the primary tumor: in this case lung metastasis inhibition index reached 97.4%. CONCLUSION: High immunogenecity of new XCV creates perspectives for detailed study of its mechanisms of action.

Xenogenic cancer vaccines.

In the current review the latest literature data on design of cancer vaccines on the basis of xenogenic tumor-associated antigens and proteins that play an important role in tumor progression have been summarized. The main benefits and disadvantages of xenogenic cancer vaccines, the results of experimental studies and clinical trials, and perspectives of use are analyzed.

Influence of bacterial lectins on some reactions of nonspecific immunity in sarcoma 37 transplanted mice.

AIM: To study preventive effect of cytotoxic lectin from Bacillus subtilis B-7025 on the tumor growth and nonspecific immunity in sarcoma 37 transplanted mice. METHODS: Sarcoma 37 cells were transplanted in Balb/c mice. Cytotoxic lectin (CL) was isolated from cultural fluid of B.subtilis strain B-7025 and inoculated at a dose of 0.2 mg per animal in prophylactic or combined schedule. Functional activity of macrophages was evaluated by NBT-test and the level of cytotoxicity, cytotoxic activity of splenocytes was assayed against K562 cells. RESULTS: CL administration in prophylactic or combined schedule results in inhibition of sarcoma 37 growth in mice. Stimulating effect of CL on peritoneal macrophages of sarcoma 37-bearing mice, especially at early stages of tumor growth, has been observed. At the late stage of tumor growth, the effect of lectin on cytotoxic activity of spleen mononuclear cells has been registered. CONCLUSION: Upon the use of lectin from B. subtilis B-7025, positive shifts of antitumor immunity reactions leading to tumor growth inhibition and elevation of average life span of tumor-bearing mice, have been detected.

Antitumor and antimetastatic activities of vaccine prepared from cisplatin-resistant lewis lung carcinoma.

AIM: To study antitumor and antimetastatic activities of antitumor vaccine (ATV) prepared from cisplatin (CP) sensitive and resistant strains of Lewis lung carcinoma (LLC). METHODS: The inhibition of tumor growth, and the mean survival time of the tumor-bearing animals, the number and the volume of metastases were measured as the indices of ATV efficacy. The activity of cytotoxic T-lymphocytes and natural killer cells, peritoneal macrophages (Mph), the level of tumor necrosis factor and the total proteolytic activity of blood plasma (PA) were assessed. RESULTS: ATV from CP resistant LLC prepared using cytolectin (CL) of capital VE, Cyrillic. subtilis capital VE, Cyrillic-7025 significantly inhibited growth of CP resistant tumors (by 52%) and increased mean survival time (MST) of animals (by 44.6%). The index of metastasis inhibition for ATV prepared from CP sensitive or resistant LLC was 154.5% and 227.0%, respectively. In all vaccine-treated animals, Mph activity was shown to be significantly increased. In spite of high antitumor and antimetastatic effects of ATV prepared from CP resistant LLC, PA in plasma of animals inoculated with CP resistant LLC was increased significantly upon vaccine administration.

Postoperative autovaccinotherapy for patients with gastric cancer and expression of some proteins in tumor tissue.

AIM: To study the efficacy of autovaccine in the treatment of gastric cancer and significance of molecular factors having prognostic values for disease outcome to evaluate its efficacy in clinical setting. PATIENTS AND METHODS: 150 patients with histologically proven adenocarcinoma of the stomach of stages II, III or IV were enrolled into study. 86 patients have been treated with autovaccine (AV) after operation. Expression of p53, Bcl-2, receptors of tyrosine kinase, vascular endothelial growth factor (VEGF), capital IE, Cyrillic-cadherin, alpha-catenin and beta-catenin was determined in paraffin embedded tumor samples by means of immunohistochemical method with the use of respective monoclonal antibodies. RESULTS: It was shown that application of AV has resulted in the increase of 3-year overall survival of patients having stage III of disease by more than 30%, but those having stage IV - only around 14%. The increase of 3-year overall survival of patients with metastases in lymph nodes (N1-2) was observed also in more than 30%. It has been suggested the optimal phenotype for vaccine application: small er, Cyrillic53(+), EGFR(+), HER-2 neu (+), beta-catenin (+), VEGF(+) and Bcl-2(+) with no dependence on E-cadherin and alpha-catenin presence. CONCLUSION: It was determined that the best effect of AV application is observed in patients with category capital TE, Cyrillic3-4, poorly-differentiated tumors, metastases in lymph nodes (N1-2), but without distant metastases (capital EM, Cyrillic0). Gastric cancer patients with p53, EGFR, HER-2/neu, beta-catenin, VEGF and Bcl-2-positive tumors are the favorable group for the treatment with AV in the adjuvant regime.

Elevation of efficacy of cancer vaccine combined with interferon and inducer of endogeneous interferon synthesis amixin.

AIM: To study in vivo efficacy of combined administration of cancer vaccine (CV), interferon (IFN) and inducer of endogenous IFN - amixin. MATERIALS AND METHODS: Sarcoma-37 cells were transplanted to female Balb/c mice. For the treatment, CV prepared from sarcoma-37 cells with the use of cytotoxic lectines from B. subtilis B-7025, murine IFN and amixin or their combinations were used. IFN production, content of circulating immune complexes and level of specific IgG antibodies in blood serum were determined by standard immunologic methods. RESULTS: Using solid form of sarcoma-37 it has been shown that introduction of IFN and amixin significantly elevated efficacy of vaccine therapy, in particular index of tumor growth inhibition reach 89.2% and 81.7%. Upon combined use of CV and IFN or CV and amixin (25 mg/kg) respectively. Significant prolongation of average life span of the animals treated with CV and IFN or CV and amixin (25 mg/kg) has been registered (up to 92.7 -/+ 10.4 and 95.0 -/+ 6.2 days respectively, vs 46.8 -/+ 1.5 days for control animals). CONCLUSION: Obtained results have shown expediency of the development of schemes for combined introduction of CV with exogenous IFN, and with inducer of endogenous IFN (amixin) for elevation of efficacy of vaccine therapy.

Influence of teichoic acid from S. aureus on metabolic activity of macrophages and cytotoxic activity of splenocytes of mice bearing Lewis lung carcinoma.

AIM: To investigate the effect of teichoic acid (TA) from the cell wall of S. aureus on some indices of immunological reactivity in mice bearing Lewis lung carcinoma (LLC). METHODS: The teichoic acid at the doses of 1, 2 and 4 microg/g of body weight has been administered subcutaneously simultaneously with tumor cells transplantation and in 7 days. The cytotoxic activity of peritoneal macrophages has been assessed by NBT-test. The splenocyte cytotoxic activity against the LLC cells has been tested by flow cytometry. The evaluation of tumor infiltration by lymphoid cells was carried out as well. RESULTS: TA had no significant effect on oxidative metabolism of peritoneal macrophages in tumor bearing mice. Upon TA administration, the cytotoxic activity of splenocytes against the LLC cells has been augmented in a dose-dependent manner (at the TA dose of 4 microg/g, 2-fold decrease of tumor growth and metastasis has been registered) and leads to decreased tumor infiltration by mononuclear cells. CONCLUSION: TA caused a dose dependent inhibition of growth and metastasis of LLC. It was supposed that TA can influence the tumor grows by activation of splenocytes cytotoxic activity.

Experimental study of the efficacy of combined use of cancer vaccine and interferon.

AIM: To study in in vivo model the efficacy of combined scheme of administration of cancer vaccine (CV) and interferon (IFN). MATERIALS AND METHODS: Lewis lung carcinoma (LLC) was transplanted to male C57Bl mice. For treatment, CV prepared from LLC cells with the use of cytotoxic lectins of B. subtilis B-7025, and preparation of murine IFN-alpha were used. Therapeutic effect was evaluated by measurement of tumor volume and analysis of average life span (ALS) of treated animals. Immunologic study included determination of antitumor cytotoxicity of T-lymphocytes (CTL) and natural killer (NK) cells by radiometric method, functional activity of peritoneal macrophages (MP) - by colorimetric test with nitroazole blue, and evaluation of titers of tumor necrosis factor (TNF) and interleukins-1 and -2 (IL-1, 2). RESULTS: It has been shown that the use of IFN preparation significantly elevated efficacy of vaccine therapy of solid form of LLC: duration of latent period of tumor growth elevated by 25%, ALS - by 28%, index of tumor growth inhibition - by 35-40%. Upon combined use of CV and IFN, significant activation of the cells - effectors of nonspecific immune defense (MP), and specific one (CTL) was observed. CONCLUSION: The obtained results evidence on perspectiveness of the development of combined schemes of administration of CV and IFN for elevation of the efficacy of vaccine therapy.

Effect of the visible light irradiation of fullerene-containing composites on the ROS generation and the viability of tumor cells.

AIM: To study the effect of fullerene-containing composites, irradiated by visible light, on the radical oxygen species (ROS) generation in thymocytes, ascitic cells from Erlich's tumor and leukemia cells L1210; to investigate viability of these cells in the presence of fullerene-containing composites under irradiation conditions. MATERIALS AND METHODS: The viability of cells was evaluated by staining with 0.4% solution of the trypan blue; ROS were detected with the use of electron paramagnetic resonance (EPR) spectroscopy and spin traps; solutions of fullerene-containing composites were irradiated with mercury-vapor lamp. RESULTS: We demonstrated that under irradiation conditions fullerene-containing composites increase the rate of ROS generation and decrease the number of viable tumor cells. CONCLUSIONS: The obtained data allow to consider the fullerene-containing composites as potential agents for photodynamic therapy.