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Oncolysis by Clostridia. III. Effects of Clostridia and Chemotherapeutic Agents on Rodent Tumors

( Merck Institute for Therapeutic Research, Rahway, New Jersey)

Intravenously injected spores of a number of species of nonpathogenic clostridia localized and germinated in tumor tissue but not in normal tissues of the mouse. In tumors of sufficient size liquefaction of an apparently substantial amount of viable tumor tissue occurred leading to statistically significant reduction of tumor weight in treated animals. Conditions for the quantitative measurement of clostridial oncolysis of Sarcoma 180 are described. Even extensive lysis did not lead to permanent eradication of the tumor in the majority of animals. With synchronously grown cultures of clostridia it has been shown that all growth phases of the microorganism were equally effective in producing oncolysis of solid tumors on intravenous injection.

In hamsters bearing the amelanotic Melanoma #4, clostridial spores localized rapidly in the tumor and produced almost complete liquefaction in a short time, although the animals usually died at the height of the lysis. In hamsters bearing the renal adenocarcinoma, the extent of lysis was variable and limited. There was no evidence of localization of organisms in small primary tumors or in metastases.

Treatment of Sarcoma 180 with clostridial spores in combination with a number of chemotherapeutic agents has been tested. A series of antimetabolites, quinones, and peroxides did not improve the effect of the spores. Improvement of clostridial oncolysis has been observed in combination therapy with 5-fluorodeoxyuridine. Combination with alkylating agents of the ethyleneimino type also significantly improved the effect on tumor weight reduction but also led to increased toxicity. By suitable adjustment of drug therapy improved results could be obtained without prohibitive toxicity.

Received 6/16/63.

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