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Combination of Local Irradiation with Systemic Application of Anaerobic Corynebacteria in Therapy of a Murine Fibrosarcoma¹

Section of Experimental Radiotherapy, University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, Houston, Texas 77025

We studied whether local irradiation of a syngeneic fibrosarcoma in C3Hf/Bu mice could be made more effective by treating the tumor hosts with Corynebacterium granulosum or Corynebacterium parvum. Tumors were generated by transplanting fibrosarcoma cells into muscles of the right thighs or into the skin in the right flank of mice. When the tumors in the thighs grew to 8 mm in diameter, they were irradiated with 2500 or 3500 rads of -rays. C. granulosum (0.5 mg i.p.) was injected into the mice 3 to 4 days before irradiation or at 3 hr or 2, 7, or 14 days after irradiation. Irradiation alone with 2500 rads induced permanent regression of only 18% of tumors. C. granulosum increased curability to between 27 and 50%, depending upon the time of treatment with the bacterium. The treatment with C. granulosum did not change the effectiveness of 3500 rads: 80% cures compared with 82% in mice that received local irradiation. Doses of 0.5 mg and 0.25 mg C. granulosum given i.p. and i.v., respectively, and 0.25 mg of C. parvum given i.v. about 3 hr after local irradiation reduced the dose of irradiation yielding local tumor control in 50% of animals which was 3400 rads in control mice by about 1000 rads.

Fibrosarcomas growing in the skin were irradiated with 2200 rads when 6 mm in diameter. C. granulosum (0.25 mg i.v.) was given about 3 hr after irradiation. Irradiation induced 25% permanent cures, C. granulosum gave 77% permanent cures and the combination of the 2 cured all treated mice.

Animals in which tumors were not controlled locally were less likely to develop pulmonary metastases if they had received adjuvant immunotherapy; only 4% of mice with local recurrence after irradiation alone were free of pulmonary metastases compared with 19% of those animals treated with irradiation and anaerobic corynebacteria.

¹ This investigation was supported by USPHS Research Grants CA 11138 and CA 06294 from the National Cancer Institute.

Received 11/11/74. Accepted 2/ 5/75.