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.

The effect of a bacterial vaccine on tumors and the immune response of ICR/Ha mice.

This study examined the effect of mixed bacterial vaccine (MBV), a biological response modifier prepared from Streptococcus pyogenes and Serratia marcescens, on the immune system of mice and on the regression of a transplantable mouse tumor sarcoma 37. The study examined MBV's biological properties and analyzed its chemical composition. The chemical composition varied with the growth media. A typical centrifuged, dialyzed supernate of the serum-containing preparation was found to consist mainly of protein and minimal amounts of carbohydrate and endotoxin, while MBV made with synthetic medium contained similar amounts of all three. MBV was nontoxic for mice, which gained weight following the injection of 0.5-1.0 ml of MBV. MBV caused regression of 20-100% of well-established mouse tumors without appreciable toxicity. MBV also had a striking effect on the immune response of mice to sheep red blood cells. When administered simultaneously with antigen injection, MBV increased the number of antibody-secreting splenocytes measured by the plaque-forming assay threefold. Serum antibody levels also increased two- to threefold. MBV did not enhance the immune response to pneumococcal polysaccharide type III, a B-cell-dependent response. However, the in vivo administration of MBV increased the in vitro response to MBV and the B-cell mitogen lipopolysaccharide. MBV compares favorably with other biological response modifiers because of its enhancing effect on the immune response and its oncolytic properties at nontoxic levels.

An immunosuppressive lipoprotein fraction from TEPC-183 bearing mice.

Lipoprotein (LP) fractions prepared from sera of normal and plasmacytoma (TEPC-183) bearing mice, were compared with respect to their effect on the in vitro anti-2,4,6-trinitrophenyl plaque forming cell response. Very low density lipoprotein (VLDL) and low density lipoprotein (LDL) fractions of sera from the plasmacytoma bearing mice contained immunosuppressive activity that was absent in VLDL and LDL fractions of normal serum LP fractions. The suppressive activity did not correlate with cholesterol or triglyceride content. Crossed-immunoelectrophoresis and polyacrylamide gel electrophoresis revealed components of the suppressive VLDL and LDL fractions which were not present in normal serum LP fractions, suggesting a modification of serum LPs by the plasmacytoma.

Tumor induction by Moloney sarcoma virus in athymic nude mice.

Athymic nude (nu/nu) mice, normal NMRI (plus/plus) mice, and nu/plus heterozygotes, inoculated at birth with the Moloney strain of murine sarcoma virus (M-MSV), did not differ either in tumor growth rate or incidence or in mortality due to tumor development; neither did nude (nu/nu) and normal NMRI mice inoculated with M-MSV at 30 days of age differ in the initial tumor growth rate. However, tumors induced in adult nude mice grew progressively and eventually killed the hosts, whereas tumors induced in adult normal NMRI mice completely regressed. These results indicated that thymus-dependent immunity, though not active in M-MSV tumor induction, determined whether the tumor, once formed, would regress or kill the host.

The effect of plasmacytomas on serum immunoglobulin levels of BALB/c mice.

The effect of tumor growth on serum immunoglobulin levels and on the immune response to sheep erythrocytes (SRBC) was studied in BALB/c mice bearing MOPC-315 (IgA), MOPC-460 (IgA), MOPC-173 (IgG2a) and MOPC-104E (IgM) to gain insight into the immunologic competence of the plasmacytoma-bearing host. The initial increase of myeloma protein coincided with the first appearance of the tumor and increased as the tumor progressed. However, at the time of death there was little correlation between spleen weights, tumor size, and myeloma-protein levels. The mean serum concentration of the myeloma proteins reached a higher level in the mice bearing tumors transplanted i.p. compared to those with tumors transferred subcutaneously (s.c.). Non-myeloma immunoglobulin levels in the serum were reduced: IgM was significantly lowered in the presence of MOPC-315 injected i.p. and MOPC-460 injected s.c. and the IgG2 levels were depressed in mice injected i.p. with MOPC-315 and MOPC-104E. The only significant reduction of IgA levels was seen when MOPC-173 was transplanted i.p. The decreases observed in immunoglobulin levels correlated with plasmacytoma growth. They were specific for myeloma and were not due to tumor growth per se since the levels of all immunoglobulins tested increased in the presence of Sarcoma 37, a pleomorphic neoplasm. The primary plaque-forming cell (PFC) response of tumor-bearing animals after the injection of 0.5 ml of 10% SRBC was either similar or enhanced compared to the controls. However, with a lower SRBC dosage (0.5 ml of 2% SRBC) the indirect PFC were reduced with mice bearing MOPC-104E and MOPC-173. Tumor sizes did not seem to correlate with reduction of the PFC response. MOPC-460-bearing mice had a comparable number of PFC per spleen to those of the controls, but reduced numbers when calculated per 10 spleen cells. Consistently, hemagglutination titers were reduced in all tumor-bearing animals. The number of direct and indirect PFC per spleen was increased in mice bearing Sarcoma 37, compared to the controls. The possible implications of these findings are discussed.

Effects of poly(2'-O-methyladenylic acid) on susceptibility and autogenous immunity to RNA tumor virus oncogenesis in vivo.

Poly(2'-O-methyladenylic acid) [poly(Am)] inhibited tumor development and death induced by the Moloney sarcoma virus-leukemia virus complex in newborn mice. The compound was effective at 10 mug per mouse when given at least 1 hr before inoculation of virus, but the greatest inhibition was seen in mice treated at least 4 hr before infection. Poly(2'-O-methyluridylic acid) and poly(vinyladenine) also inhibited sarcoma development and death but were less effective than poly(Am). Poly(Am) also enhanced the antibody response of newborn mice to endogenous leukemia virus envelope antigens, which we refer to as autogenous immunity. The results of these preliminary studies suggest that poly(Am) altered the oncogenic potential of the Moloney sarcoma-leukemia virus complex in vivo, and the effect appears to be mediated through an enhancement of the immune response of the treated animals.