Summary
The resistance to Ehrlich ascites tumour transplants in mice immunized with live Salmonella enteritidis 11RX was investigated. In mice still carrying the bacterial infection, the resistance appeared to be attributable to an increase in both the number and the anti‐tumour activity of the peritoneal cells. This activity was demonstrated in vivo run by the rapid removal of tumour cells from the peritoneal cavity and in vitro by the cytolysis of tumour cells. The spleen cells of resistant mice did not possess these properties.
Summary
In vivo and in vitro parameters of tumour resistance were examined after immunization of mice with the attenuated 11RX strain of S. enteritidis. During the bacterial carrier state produced by intraperitoneal (i.p.) or intravenous (i.v.) injection of 11RX the mice were resistant to i.p. tumour growth, could destroy i.p. injected 125I‐ or 131I‐labelled tumour cells in vivo and had non‐specifically cytotoxic peritoneal cells (PC) which could lyse 51Cr‐labelled tumour cells in vitro. Most of the in vivo and in vitro cytotoxic activity could be attributed to activated macrophages (La Posta et al., 1982). The predominantly local nature of 11RX‐induced anti‐tumour activity was indicated by the superiority of the i.p. route of infection for induction of tumour resistance and in vivo and in vitro cytotoxicity.
After i.v. injection of 11RX, none of the anti‐tumour effects outlasted the bacterial carrier state. However, after i.p. infection, a dichotomy was observed between in vitro and in vivo anti‐tumour effects. In vitro PC cytotoxicity lasted only for the length of the 11RX carrier state (approximately 30 days), whereas resistance to i.p. tumour growth lasted for 60 to 100 days and was correlated closely with cytotoxic activity measured in vivo. Possible reasons for this dichotomy are discussed.
A majority of guinea pigs, each with a growing syngeneic tumor implant in the skin and no other outward sign of malignancy (clinical stage I disease) but with tumor cells in the regional lymph nodes, was cured by tumor-specific immunization after limited surgery consisting of excision of the dermal tumor (1, 2). Animals treated by limited surgery alone were not cured; they developed palpable tumors in the draining lymph nodes, and at autopsy, 70-80% of the animals were found to have pulmonary metastases (3) . We now report the results of studies to test the efficacy of limited surgery and tumor-specific immunization in the treatment of animals, each with a dermal tumor and a palpable draining lymph node (clinical stage II disease) . We also tested limited surgery and immunization for the treatment of animals with clinical stage II disease and pulmonary tumors that had been implanted intravenously . Information from these studies may be useful in the design of clinical investigations to evaluate proposed treatments for humans with cancer.
Materials and MethodsAnimals . Male Sewall Wright strain 2 guinea pigs 3-4 mo old and weighing 500-550 grams were obtained from the Laboratory Aids Branch, Division of Research Services, National Institutes of Health (NIH) Bethesda, Md . and from the Experimental Animal Breeding Facility of the National Cancer Institute, Frederick Cancer Research Center, Frederick, Md . Caged in groups of six, the animals were maintained on a diet of NIH guinea pig ration and filtered tap water, which were available to the animals at all times.Tumor Line . We used a transplantable, syngeneic hepatocellular carcinoma-designated line 10 (L10)'-in transplant generations 9-19 . This diethylnitrosamine-induced tumor has been converted to ascites form and is passed intraperitoneally in weanling strain 2 guinea pigs . Inoculation of 10 6 L10 tumor cells intradermally in the flank 2 cm posterior to the axillae of animals that are left untreated leads to progressive intradermal tumor growth, metastasis of tumor cells to draining lymph nodes, and death. At autopsy, 30-40% of the animals are found to have gross, visible pulmonary metastases (3). Limited surgery designed to remove the dermal tumor and to leave microscopic lymph node metastases in place is not curative, but prolongs survival of the guinea pigs ; at autopsy, the majority of them are found to have pulmonary as well as lymph node metastases (3).
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.