Trypanosoma cruzi Endotoxin (KR) in the Treatment of Malignant Mouse Tumors

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Abstract
Eight strains of T. cruzi were tested against 5 vars. of malignant tumors in over 1,300 mice. The trypanosomes covered a wide range of virulence and were derived from various mammalian and insect hosts. The tumors were: transplantable sarcomas 37 and 180 in Swiss and A-mice; transplantable squamous cell carcinoma 119 in A-mice; transplantable and spontaneous mammary ade-nocarcinoma in C3H and dba mice. Infections with T. cruzi strains, i.e., active Chagas'' disease, produced consistent inhibition of tumor growth, but caused very few tumor regressions and generally did not prolong life of infected cancerous mice beyond that of controls. Loss in body wt. often accompanied inhibition. Wt. losses were correlated with the graded virulence of the strains. The parasites were not "positively tumerotropic." Cancer cells proper were only rarely parasitized. The infection was lightly present in the stroma of some tumors and was heavily concentrated in heart, liver, spleen, kidney, small intestine, and skeletal muscle. Cancerous mice infected with the always lethal W-BH strain died within 8-13 days of inoculation. Wt. loss was considerable, and tumor growth was almost completely suppressed. When the infection was checked with Bayer 7602, the previously inhibited tumors resumed their usual growth, and the hosts died of cancer. Tumor inhibition by living T. cruzi may be attributed to competition for dietary factors and to general depletion of the host-system by the infection. Active Chagas'' disease has, thus, no value in treating malignant growths. Cultures of T. cruzi (Brazil strain) were heat killed and injected intraperit. into cancerous mice, or the tumor pieces were soaked in the prepns. for 8 hrs. before implanting. Injns. were without effect. The latter pretreatment did not reduce the number of "takes" or change growth. Concns. of T. cruzi cen-trifuged from cultures of B-strain in NIH medium or from the plasmas of mice bled at the height of infection with W-BH strain were lysed by addn. of neutral glass-dist. water and extracted at 1 C for 24 hrs. before use. The lysate when injected was 1-6 days old. The lysate was sterile, and from 8-16 daily injns. were given. It produced no tumor regressions, but occasionally damaged neoplastic and normal tissues. Mortality was greater in treated mice than in controls. Mali-soff (1947) modified the technic by adding dist. water and 1:10, 000 Metaphen to whole cultures of the S strain grown on NNN medium with Tyrode overlay. These were injected intraperit. or subcut., and were quantitated to give the equivalent of 1 million lysed organisms/ daily inoculum. These cultures were tested on 2 tumors, Sugiura S-180 and Malisoff''s sarcoma T-180. The former took and killed in all cases, while the latter regressed spontaneously in over half the controls. "Whole culture lysates" tested against spontaneous adenocarcinoma in C3H and dba mice had no cancerolytic effect and did not prolong survival.

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