Treatment of inbred rats with a methanol-soluble fraction of phenol-killed Mycobacterium butyricum (MSF-MB) markedly enhanced their immunological response to subsequent immunization with sheep red blood cells. Optimal timing and dosage for MSF-MB treatment were determined. Enhancement of the immune response by MSF-MB, at the optimal dose level of 10 mg/rat, was reflected in peak antibody titer 14 days after MSF-MB treatment. If MSF-MB was administered 7 days prior to antigenic stimulus, peak titer was attained on Day 7; MSF-MB administered simultaneous with or 2 to 4 days after challenge resulted in peak titer on Day 14. In addition to the heightened immunological responsiveness, MSF-MB had the capability of maintaining the immune response of the host at a high level for 4 weeks following immunization, indicating a prolongation of antibody systhesis in addition to an accelerated rate of synthesis.
Tumors resulting from grafts of two mammary adenocarcinomas (13762 and R-35), a prostatic, squamous cell carcinoma (11095) and an acute monocytic leukemia (R3149), exerted an immunosuppressive effect on heteroantibody response when the hosts were challenged with sheep erythrocytes during the early or midlog phase of tumor growth. MSF-MB administered to rats bearing the above tumors 7 days prior to antigenic stimulation, at early or midlog growth phase, not only completely abrogated the immunosuppression of tumor growth but also significantly enhanced the primary hemagglutinin response in the R-35 and R3149 tumor systems. The effect of MSF-MB treatment on the transplantation and growth of rat transplantable mammary adenocarcinomas was variable and closely related to the time of its administration. The use of the adjuvant during chemotherapy and consequent oncolysis and tumor resorption appears to have nonspecifically enhanced host responses and augmented the antitumor effects of chemotherapy.
This investigation was supported by Contract Ph43-63-1146 from the Endocrine Evaluation Branch, National Cancer Institute, General Laboratories and Clinics, NIH.