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Bacillus Calmette-Guérin Cell Wall Immunotherapy of Intramuscular and Metastatic Morris Rat Hepatomas¹

Veterans Administration Hospital, San Diego, California 92161 [H. T. W.]; Departments of Pathology [H. T. W., S. S.] and Biology [R. S. T.], School of Medicine, University of California, San Diego, La Jolla, California 92093; Veterans Administration Hospital and University of San Antonio Medical School, San Antonio, Texas 78284 [S. H.]; Rocky Mountain Laboratory, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840 [E. R.]; and Howard University College of Medicine, Washington, D. C. 20059 [H. M.]

Treatment with Bacillus Calmette-Guérin cell walls attached to oil droplets (BCGcw) has little or no effect upon the growth of antigenic transplantable Morris hepatoma tumors, either of tumors growing at the i.m. site of tumor inoculation or of metastatic lesions in the lungs. When tumors weighing approximately 1 g were given injections directly on Day 10, 2 of 20 animals demonstrated regression of tumor growth, whereas injections into larger tumors (greater than 2 g) on Day 14 had no effect upon tumor growth. We performed three types of experiments using tumor lines 7777 and 5123tc to evaluate the effect of BCGcw immunotherapy upon the growth of tumor metastases. In Experiment 1, tumor line 7777 i.m. masses were amputated at a time when lung metastases would develop, and BCGcw were administered i.v. after amputation of the transplant site. Five of 27 (18%) of the animals treated with surgery only, and 9 of 57 (16%) of BCGcw-treated animals, survived free of metastases. With the use of the serum concentration of ₁-fetoprotein to follow tumor growth, it was possible to demonstrate that sometimes established metastases regressed following BCGcw immunotherapy. In Experiment 2, "artificial" lung metastases were induced by the i.v. inoculation of either 1 x 10⁶ or 5 x 10⁵ tumor cells. Three to 6 hr later, animals were inoculated i.v. with 150 µg of BCGcw. This treatment had no effect upon the growth of metastases or upon the survival of animals. In Experiment 3, the inoculation of BCGcw into intrafootpad tumors prior to surgical excision also had no effect on metastatic tumor growth or survival. These studies suggest that BCGcw immunotherapy may not be effective upon the transplantable Morris hepatoma tumors studied.

¹ Supported by the Medical Research Service of the Veterans Administration, Veterans of World War I, Department of California, and by NIH Grant CA 10729 and NIH Training Grant CA 09174.

² To whom requests for reprints should be addressed, at Department of Pathology/Research (151), Veterans Administration Hospital, 3350 La Jolla Village Drive, San Diego, Calif. 92161.

Received 5/13/77. Accepted 1/27/78.