No abstract

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 production of antibodies that react with the Fc fragment of IgG, i.e., rheumatoid factors (RF), is now regarded as a normal host immune response. It is not clear, however, if such putative physiologic RF are different from their counterparts which characterize pathologic states like rheumatoid arthritis (RA). Using Staphylococcus aureus Cowan I as an in vitro stimulant of RF production, we now report that the IgM‐RF secreted by blood mononuclear cells obtained from healthy newborn infants and healthy adults can be distinguished not only from classic monoclonal RF and polyclonal RA serum RF, but also from the RF secreted by blood mononuclear cells obtained from RA patients. Whereas the Fc‐binding activity of all RF secreted in vitro was easily inhibited by aggregated human IgG, only the RF produced by the normal umbilical cord cells and the normal adult cells were inhibited by monomeric Fc(IgG). The normal RF were also selectively inhibited by monomeric rabbit and guinea pig Fc(IgG). The RF secreted by umbilical cord blood cells utilized λ and λ light chains, with a disproportionate use of λ light chains relative to the total IgM secreted. Together, these data provide evidence for distinct subsets of RF in health and in disease.

We previously reported that Staphylococcus aureus Cowan I (SAC) is a potent stimulant of IgM rheumatoid factor (RF) production by normal adult peripheral blood mononuclear cells. In the current study, we compared the capacity of normal adult peripheral blood mononuclear cells and cord blood mononuclear cells to produce IgM RF. Although both populations of cells consistently produced IgM RF in response to SAC, the quantity of RF produced by cord blood cells (128 +/- 18 ng/ml, mean +/- SEM) greatly exceeded that of adult cells (37 +/- 5 ng/ml, p less than 0.0005) even though both populations of cells demonstrated comparable total IgM responses. Remarkably, 16.7% of total IgM produced by cord blood cells in response to SAC showed RF activity compared to only 3.4% (p less than 0.0001) of the total IgM produced by SAC-stimulated adult cells. Thus, precursors of IgM RF-secreting cells are not only a consistent feature of the normal adult human B cell repertoire, but they are especially represented at the time of birth. These findings are consistent with the hypothesis that IgM RF originates from germ line genes and underscore the utility of SAC as a probe for analyzing the production of this autoantibody.