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The Distribution and Persistence in Vivo of Corynebacterium parvum in Relation to Its Antitumor Activity

Department of Experimental Immunobiology, Wellcome Research Laboratories, Beckenham, Kent BR3 3BS, England, [M. T. S.] and Department of Radiotherapy, The University of Texas Cancer Center, M. D. Anderson Hospital and Tumor Institute, Houston, Texas 77025 [L. M.]

Killed Corynebacterium parvum was labeled with fluorescein isothiocyanate or ¹²⁵I, and both preparations were shown to retain lymphoreticular stimulatory and antitumor activity. Large amounts of C. parvum injected i.v. were found in the liver, spleen, and lungs with less in bone marrow and lymph nodes. Apart from a rapid loss from the lungs within 24 hr, the persistence of killed C. parvum was striking, and some intact bacteria were still detectable in the liver and spleen at 15 days. (By contrast, the breakdown of an inactive C. parvum strain in the liver was considerably faster.) The blood clearance of ¹²⁵I-labeled C. parvum injected i.v. into tumor-bearing mice was more rapid than in normal mice, and the absolute, but not the unit, amounts of C. parvum taken up by the spleen and tumor-draining node were increased. ¹²⁵I-labeled C. parvum was found within the body of established solid tumors, but there was no correlation between the amount of C. parvum taken up by various mouse solid tumors after i.v. injection and their susceptibility to i.v. C. parvum therapy. The distribution and persistence of C. parvum injected into a tumor lesion was similar to that after s.c. injection. The bulk of the inoculum was retained at the injection site and draining lymph node. Contralateral nodes were unlabeled, and uptake in the liver and spleen was considerably less than after i.v. injection. Although no C. parvum was found in peritoneal cells after i.v. injection, the macrophages in this population became activated and were capable of nonspecifically inhibiting tumor cell growth in vitro.

¹ To whom requests for reprints should be addressed.

² Present address: Central Institute for Tumor and Allied Diseases, Zagreb, Yugoslavia.

Received 11/23/76. Accepted 3/ 3/77.

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