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Effects of Dose and Schedule of Immune Stimulant on Efficacy of Combination Corynebacterium parvum-Cyclophosphamide Treatment for a Murine Mammary Adenocarcinoma¹

Department of Pathology, School of Medicine, University of Maryland, Baltimore, Maryland 21201 [D. M. P.], and the Departments of Pathology and Microbiology and Specialized Cancer Research Center, College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania 17033 [G. L. B., J. W. K.]

Certain variables which might influence the outcome of combining cytotoxic drug and immune stimulant therapy were studied to optimize the effectiveness of Corynebacterium parvum combined with cyclophosphamide (CY) as treatment for a murine mammary adenocarcinoma (CaD₂). Optimal effects of combined C. parvum-CY treatment in the CaD₂ system were obtained when 443 to 1400 µg of this immune stimulant per mouse were injected 2 to 3 days after CY chemotherapy and when combination treatment was continued on a weekly basis. The most critical factors contributing to the effectiveness of combination treatment in this system were the dose of C. parvum and the treatment frequency. The interval between chemotherapy and immune stimulant therapy was less critical to the outcome of combination treatment. Combination treatment given once or weekly significantly decreased tumor size in comparison to single or weekly CY treatment. A single treatment with CY and C. parvum significantly improved the survival over mice given a single CY treatment, but weekly CY and C. parvum treatment did not increase the survival over mice, given weekly chemotherapy.

¹ Supported by Contract N01-CB-33891 and Grant P30-CA-18450 from the National Cancer Institute and by funds from the Jake Gittlen Memorial Golf Tournament.

² To whom requests for reprints should be addressed.

³ Recipient of USPHS Career Development Award K04-CA-70948 from the National Cancer Institute.

Received 5/25/78. Accepted 9/26/78.