Immunotherapy of a plasmacytoma with attenuated salmonella.

An attenuated strain of Salmonella typhimurium, SL3235, developed as a prototypic typhoid vaccine, is shown to retard growth of a murine plasmacytoma, TEPC-183, and to prolong survival of tumor-bearing mice. Live salmonella, but not acetone-killed organisms, had antitumor activity. The immunotherapeutic effect was demonstrable when the tumor was injected intralesionally or intraperitoneally. Increased survival, longer mean time to death, and retardation of tumor growth were found when the salmonella were given intralesionally as late as the sixth day post-tumor injection. Timing of salmonella inoculation, as well as the salmonella dose, had an effect on treatment efficacy. Injection of salmonella intraperitoneally exerted a strong antitumor effect when given as late as the third day post-tumor inoculation. The highest dose (2 x 10(6)) of salmonella was less effective than doses 10- or 100-fold lower. TEPC-183 plasmacytoma is rapidly growing and highly immunosuppressive, so the ability of the salmonella to exert therapeutic activity against it is a measure of the potency of the vaccine. These observations are of interest, as they show that a genetically engineered, avirulent strain of Salmonella has immunotherapeutic properties similar to those of BCG and other biological response modifiers, and might have clinical potential as an antitumor agent.

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.

Effect of the mixed bacterial vaccine on the immune response of patients with non-small cell lung cancer and refractory malignancies.

Since 1984, 13 patients were entered into our study and 12 patients have completed one or more cycles of treatment with mixed bacterial vaccine (MBV), a natural biologic response modifier derived from Streptococcus pyogenes and Serratia marcescens. Eight patients with refractory malignancy were treated with MBV only (0.1 ml intravenously [IV]) twice weekly for 3-16 weeks (colorectal cancer, pancreatic cancer, chronic lymphatic leukemia, hepatoma [two patients], sarcoma [three patients]). Four patients with advanced non-small cell lung cancer were treated with MBV in combination with low-dose cyclophosphamide, day 1; cisplatin, day 15; and MBV, 0.1 ml IV, days 5, 7, and 9. Two patients in this study received cyclophosphamide and cisplatin alone. The cycle was repeated every 28 days. Plasma interferon levels, interleukin-2 production by peripheral lymphocytes, and lymphocyte subpopulations were monitored. Interferon levels and interleukin-2 production showed increased or sustained values in general. In some patients, B-cells and helper T-cell populations increased, whereas T-suppressor cell numbers declined. With one exception, side effects were mild and consisted of fever greater than 37.8 degrees C (nine of 13), chills (11 of 13), increased respiratory rate (nine of 13), minor changes in blood pressure (seven of 13), and nausea (three of 13). One patient with non-small cell lung cancer had a partial response. Two patients with non-small cell lung cancer and one patient with refractory malignancy had stable disease and performance status at the end of 8 weeks of treatment; one patient with refractory malignancy was stable at the end of 4 weeks of treatment. In this pilot study, cancer patients treated with MBV showed objective evidence of immune stimulation with acceptable toxicity.

Enzootic mycoplasmal mastitis in a large dairy during an eight-year period.

During an 8-year period, a study was conducted in a large dairy in the Sacramento Valley of California, to define factors associated with the introduction and spread of mycoplasmal mastitis. To identify cows in which mycoplasmal infection appeared in 22 of 25 (88%) periods of new infection, milk samples were collected weekly from freshened cows and from hospitalized cows with clinical mastitis. The disease first appeared in freshened cows in at least 36% of the periods of new cases of mycoplasmal mastitis, which indicated that special attention must be paid to freshening cows in an attempt to control spread of the disease. New cases of mycoplasmal mastitis were recorded more often in January through April than during the rest of the year. Rates of mastitis infection caused by other pathogens (contagious and environmental organisms) increased during months when new cases of mycoplasmal mastitis were recorded. Sanitation on the farm during udder infusion and milking was a major factor in controlling the introduction and spread of mycoplasmal mastitis.