Corynebacterium parvum: Effect on radiocurability of murine tumors

Abstract

In continuation of our earlier studies (Milas et al., 1975c) we have investigated whether treatment of mice with Corynebacterium parvum augments the curative response of a fairly immunogenic fibrosarcoma (FSa) and a weakly immunogenic mammary carcinoma (MDAH-MCa-4) to fractionated v-irradiation. Tumors were 8 mm in diameter at the commencement of radiation treatment. The FSa was exposed to 500 and the MDAH-MCa-4 to 750 rads daily for 3, 6, or 10 consecutive days. The dose of CP was 0.25 mg and was given intravenously (IV), in most experiments within 2 h after the first irradiation dose. In one experiment involving FSa, CP administration varied from 4 days before to 14 days after the start of irradiation. CP greatly augmented FSa radiocurability, especially when applied before irradiation. The effect was evident from the increase in the cure rate, and, in mice that were not cured, from tumor growth retardation, which resulted in prolonged survival of mice. CP also reduced the incidence of pulmonary metastases in mice in which the combination of treatments failed to produce local tumor control. CP was less effective in augmenting radiation response of MDAH-MCa-4. In this case, CP slowed the growth of irradiated tumors and prolonged the survival of mice. The effect of IV CP on FSa radiocurability was not further increased by including intralesional (IL) injection of CP, intraperitoneal (IP) injection of vitamin A, or the radiosensitizer of hypoxic tumor cells misonidazole (Ro-07-0582). Misonidazole, however, significantly improved the effect of 2000 rads on the growth retardation of mammary carcinoma, but CP did not further enhance this effect.