Inhibition of Tumour Growth by Administration of Killed Corynebacterium parvum

Cells from the spleen, lymph node, peripheral blood and peritoneal exudate of mice treated with C. parvum were tested for their ability to inhibit tumour growth in vitro. The peritoneal exudate cells from C. parvum treated mice were extremely effective in inhibiting tumour growth whereas the spleen and peripheral blood cells were only moderately so. In contrast, the lymph node cells caused only a modest inhibition of tumour growth at a very high effector to target cell ratio. Spleen cells from normal mice also exerted a moderate anti-tumour effect.

mentioning

confidence: 98%

Anti-Tumour Effect In Vitro of Lymphocytes and Macrophages from Mice Treated with Corynebacterium Parvum

Ghaffar¹,

Cullen²,

Dunbar³

et al. 1974

“…THERE is extensive documentation of the antitumour effect of Corynebacterium parvum on a wide variety of solid and ascitic murine tumours (Woodruff and Boak, 1966;Halpern et al, 1966;Castro, 1974) and on its inhibitory effect on naturally occurring metastases (Proctor, Rudenstam and Alexander, 1973;Castro, 1975, 1976).…”

mentioning

confidence: 99%

Effects of C. parvum on growth and induction of intracerebral tumours in mice

Osborn¹,

Sadler²,

Castro³

1977

An investigation was made into the effect of Corynebacterium parvum therapy on cerebral tumours in mice. I.v. C. parvum caused a slight but significant increase in the survival of BALB/c mice injected intracerebrally (i.c.) with not more than 50 Meth A cells. C. parvum was most effective if given on the same day or 5 days after tumour. If this interval was increased there was no effect. Multiple i.v. injections were no more effective than a single dose. I.v. C. parvum had no influence on the survival of C57BL mice injected i.c. with Lewis tumour cells, and had little effect on the induction of i.c. or s.c. tumours by methylcholanthrene. It was concluded that C. parvum therapy was of little use in the treatment of cerebral tumour in mice. The clinical implications of these findings are discussed.

“…Since the growth inhibitory effect of activated macrophages is confined to tumour cells (Hibbs, Lambert and Remm.ington, 1972) Levy (1970) has attributed the effect of dsRNA as an antitumour agent to this property. While it has been clearly shown that much more potent stimulants of the immune system than dsRNA, s-uch as mycobacteria (e.g., BCG) and (1orynebacteriunm parvum, render rodents more resistant to a subsequent challenge with tumour cells (Halpern et al, 1959(Halpern et al, , 1966Old et al, 1961), such agents have only a minor therapeutic effect when given after the tumour has been injected (Mathe, Pouillant and Rapeyraque, 1969;Parr, 1972 Tumours.-Two tumours, a lymphoma L5178Y and a fibrosarcoma FS6, were used for the majority of the experiments. Brief details of these and the other tumour lines used are given in Table I.…”

mentioning

confidence: 99%

Similarities of the Anti-tumour Actions of Endotoxin, Lipid A and Double-stranded RNA

Parr¹,

Wheeler²,

Alexander³

1973

120

Summary.-Double stranded RNA (dsRNA) whether isolated from a fungal virus or prepared synthetically (i.e., Poly I Poly C) and endotoxin were found to exert very similar effects on syngeneic murine lymphomata and fibrosarcomata. They cause complete regressions of some established subcutaneous (s.c.) or intradermal (i.d.) tumours but not of intraperitoneal (i.p.) tumours when administered either systemically or directly into the tumour. To achieve this effect the tumours must be fully established and the best results were obtained when treatment was started 7 days after transplant. If treatment is started within the first 3 days following the transplantation of the tumour then only a slight inhibition of growth rate was observed. These agents can also act prophylactically and protect mice against a subsequent challenge but only if this is given i.p. and not if given s.c. or i.d. The prophylactic action is explained by the action of dsRNA and endotoxin on peritoneal macrophages which cause them to become cytotoxic to tumour cells (i.e., to become activated).The therapeutic effect of systemically administered endotoxin and dsRNA on established tumours is not the result of a direct action on the tumour cells themselves but is a complex process requiring the co-operation of several host factors. Haemorrhagic necrosis involving coagulation is essential (i.e., heparinization reduces the regression of tumours) but is not itself sufficient. Immunosuppression by whole body irradiation or by antilymphocyte serum also interferes with the antitumour action of dsRNA and endotoxin in spite of the fact that haemorrhagic necrosis still occurs. Also, the magnitude of the antitumour action correlated in a series of different tumours with their antigenicity. The observed tumour regressions are probably brought about by (1) vascular damage in the tumour which permits immune defence mechanisms of the host to gain access to the tumour and (2) activation of macrophages present within the tumour. The relative contribution of these two mechanisms may depend on the nature of the tumour and the route of administration of the active agents.Dibenyline, which protects against the lethal action of endotoxin by preventing the action of the catecholamines on the a-adrenergic receptors, makes it possible to increase the effectiveness of endotoxin in tumours by allowing a large dose to be given. Lipid A, a derivative of endotoxin which does not contain polysaccharide, has similar antitumour action to dsRNA and endotoxin. Some common features of the chemical structure of lipid A and dsRNA are discussed.Over a hundred years ago (Busch (Coley's toxin), which contained endotoxins 1866), a Viennese physician noted that amongst many other components, and regressions of some malignant tumours achieved some very striking results (cf. appeared to coincide with the occurrence review by Nauts, Fowler and Bogatko, of erysipelas. Coley, having made a 1953). The subject of the antitumour similar observation, deliberately treated action of endotoxins has attracte...