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.

[Effect of dendritic cell autovaccine on the treatment outcome in patients with ovarian cancer].

During I/II phase clinical trial in ovarian cancer (OC) patients two types of autologous anticancer vaccines based on dendritic cells have been tested, and a comparative analysis of their effectiveness have been performed. It was shown that the anticancer vaccines based on DC, "loaded" with autologous tumor cell lysate obtained by treatment of tumor cells by cytotoxic lectins B. subtilis had higher efficiency, compared with the standard DC--autovaccine. The presence of antigen-specific immune response observed after at least four vaccinations. Obtained results open the prospects to improve the basic treatment of OC patients by this method. The results of immunological examinations create preconditions for individual optimization of the DC-vaccine therapy.

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.

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.

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.

[The efficacy of using low doses of immunomodulators for treating experimental tumors]. / Effektivnost' primeneniia malykh doz immunomoduliatorov dlia lecheniia éksperimental'nykh opukholei.

The data about the ability of various substances to cause definite reactions in biological objects are adduced, and, in particular, about the efficacy of a small doses of antitumoral chemopreparations in experiment. The results of investigation of the application efficacy of various doses of immunomodulating agents, such as arbisol, nucleoplat, the substrate from gram-negative bacteria Yersinia enterocolitica, antitumoral vaccine from the tumoral cells are presented for the cancer chemotherapy. While application of super-small doses of an antitumoral vaccine there was noted statistically significant inhibition of tumoral growth.

[Immune reaction to the heterologic test-antigen in mice with anti-cancer vaccine]. / Immunnyi otvet na geterologicheskii test-antigen u myshei, kotorym vvodili protivoopukholevuiu vaksinu.

The stimulated influence of the antitumoral vaccine, prepared with the help of filtrate of the Bacillus mesentericus AB-56 or the antibiotic, extracted from it, on the immune answer to heterologic test-antigen (ram erythrocytes) was established. While the vaccine injection to laboratory animals with developing tumor their capacity to resist to the tumors was rising up.

[Modification of 3-methylcholanthrene-induced blastomogenesis in BALB/c mice by using the subcellular components of Bac. megaterium H]. / Modifikatsiia blastomogeneza, indutsirovannogo 3-metilkholantrenom u myshei BALB/c, pri pomoshchi subkletochnykh komponentov Bac. megaterium H.

It is shown that the cytoplasm of Bac. megaterium H possessing the antigenic affinity with the malignant tumour cells, being injected 7 days before the 3-methylcholanthrene injection promotes intensification of its blastomogenic effect, reduces both the period of tumour appearance and longevity of the tumour-bearing animals. On the contrary the cell wall preparation under the similar conditions, produces a therapeutic effect. An assumption is advanced that the effect of these preparations is associated with their different influence on the immune system.

[Effect of Bac. megaterium H on tumor induction by methylcholanthrene]. / Vliianie Bac. megaterium H na induktsiiu opukholei metilkholantrenom.

It is shown that Bac megaterium H which has cross-reacting antigens with malignant tumour tissues may influence the time of appearance and growth of tumours, induced by 20-methylcholanthrene in BALB/c mice. The strengthening of tumour growth rate was most distinctly displayed if Bac. megaterium H was injected once 7 days before the methylcholanthrene inoculation.

[Possible role of Bac. megaterium H antigens common with tumor antigens in the increase of the antitumor activity of lymphocytes]. / O vozmozhnoi roli obshchikh s opukholevymi antigenov mikrobnoi kul'tury Bac. megaterium H v povyshenii protivoopukholevoi aktivnosti limfotsitov.

The antitumour cytotoxic activity of lymphocytes is shown to increase both with inoculation of antigens contained in tumour cells and under the influence of microbial Bac. megaterium H., culture, its ultrasonic homogenate, cell walls and cytoplasmic preparation. Certain cytoplasmic fractions of Bac. megaterium H, like other microbial and tissue antigens having no similarity with tumour cells, did not produce such an effect. An assumption is advanced that the increase in the antitumour cytotoxicity of lymphocytes under the influence of Bac. megaterium H is due to the cross-reacting antigens contained in the microbial cell and blastoma tissue.