Antitumor activity of bacterial infection. I. Effect of Listeria monocytogenes on growth of a murine fibrosarcoma

Abstract

Growth of a murine fibrosarcoma was suppressed when tumor cells were mixed with viable Listeria monocytogenes (LM) before intradermal injection into nonimmune syngeneic recepients. Immunization of recipients, by intravenous injection of LM 11 days before transplantation of LM-tumor cell mixtures, eliminated the mortality associated with large doses of LM but did not alter the antitumor activity of the microorganisms. Simultaneous injection of LM and tumor cells at separate sites failed to affect tumor growth, which suggested that contact between LM and tumor cells was required for tumor suppression. Tumor-specific immunity was not observed; mice surviving injection of LM and tumor cells did not resist a second tumor-cell challenge. At least 100 times more heat-killed LM was required to produce the antitumor effect of viable organisms. The ability of heat-killed LM to suppress tumor growth was abolished by treatment of recipients with rabbit antiserum to mouse thymocytes, which was consistent with a requirement for a host response to the LM. Regression of established fibrosarcoma transplants was produced by the intratumor injection of viable LM 5 days after injection of tumor cells. Intratumor injection of BCG at this interval was not effective. The incidence of tumor regression was not increased by multiple intratumor injections of LM, by intratumor injection of a combination of LM and BCG, or by preimmunization with LM prior to the intratumor injection of the same organism.