Cytotoxic activity of immune cells following administration of xenogeneic cancer vaccine in mice with melanoma B-16.

AIM: To study the effects of xenogeneic cancer vaccine (XCV) developed on the basis of nervous tissue antigen from rat embryo of late gestation period and protein-containing metabolite of Bacillus subtilis with molecular weight of 70 kDa, on specific and unspecific antitumor reactions of cellular and humoral chains of immune system, and to analyze possible mechanisms of its antimetastatic action. MATERIALS AND METHODS: XCV was administered triply with 3-day intervals after surgical removal of experimental melanoma В-16 in C57Bl/6 mice. Cytotoxic activity (CTA) of splenocytes against target cells К-562 as well as CTA of splenocytes, peritoneal macrophages (PM) and blood serum against melanoma В-16 target cells were determined using МТТ test. The content of circulating immune complexes (CIC) in blood serum was evaluated by precipitation reaction. RESULTS: Immunologic effects of XCV vaccination in experimental animals with surgically removed melanoma B-16 in comparison with similarly treated unvaccinated mice were as follows: prevention of medium molecular weight CIC accumulation in blood serum during all observation period, significant increase (р < 0.05) of CTA of effectors of unspecific antitumor immunity (natural killer cells - NK - by 25.5 ± 1.7 vs 12.5 ± 5.4%, and PM - by 37.3 ± 0.6 vs 32.0 ± 0.9%, respectively) at 37(th) day after the surgery, and also preservation of functional activity of specific cytotoxic lymphocytes at the level of intact control. CONCLUSION: The results of the study allow propose that antimetastatic effect of XCV vaccination could be based on increased CTA of NK and PM, and preservation of CTL functional activity at late terms after surgical removal of B-16 primary tumors.

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.

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.

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.