Experimental Cancer Immunotherapy: Comparison of Tumor Rejection in F344 Rats Given Live Mycobacterium bovis (Strain BCG) and Killed Corynebacterium parvum

Abstract

F344 rats received grafts of syngeneic 13762 mammary adenocarcinoma cells previously admixed with either living BCG of killed Corynebacterium parvum administered sc or intradermally (id). Animals given id transplants of tumor cells admixed with either BCG or killed C. parvum exhibited tumor growth for an average of 10 days, then regression in size and rejection of the tumor nodules. Lesions were found in rats given sc transplants of tumor cells admixed with the killed microorganism for an average of 13 days with the same results. When live BCG was added to the sc transplants, accelerated rates of tumor growth and early death were noted, compared with the group receiving tumor cells alone sc. Suppressed rates of tumor growth and prolonged survival were observed in the groups receiving id inoculations of tumor cells followed by treatment with killed C. parvum administered weekly ip or id 1 cm away and around the growing tumor. On the other hand, weekly treatment of BCG injected either ip or id 1 cm away and around the growing tumor resulted in accelerated rates of tumor growth and early death. Animals exhibiting C. parvum of BCG-mediated tumor rejection displayed tumor-specific protection to sc challenge injections of the cell line initially used, but they died with growing tumors and metastases when challenged with tumor cells of an antigenically different line syngeneic to F344 RATS. Microscopic examination of histologic sections of tumors formed from id inoculations of tumor cells admixed with either BCG or killed C. parvum revealed a nonspecific infiltrate of macrophages and polymorphonuclear leukocytes in the tumor, whereas sections of tumors formed from sc grafts of cells admixed with killed C. parvum revealed a specific organized infiltrate of mostly macrophages around the tumor follicles.

Experimental screening of two BCG preparations produced according to different principles

“…Our results contrast with the results of these authors, but confirm the results of Tokunaga et al [32], who also found no effect in some mouse models and the results of Likhite [18], who found growth enhancement in a rat tumor model. The mechanism of BCG-induced tumor growth enhancement is not yet clarified.…”

C. Parvum immunotherapy of transplanted rat tumours

“…sarcomas Mc7 and Mc40A, animals rejecting mixed tumour cell: C. parvum inocula were immune to rechallenge but this was not apparent with the more moderately immunogenic hepatoma D23 where challenge inocula of 5x105 cells can be rejected by pre-immunized rats while animals rejecting tumour cells and C. parvum were not immune to 5 X lo3 cells. Studies in other species have shown similar patterns of reactivity, so that injection of tumour cells in admixture with C. parvum, or intralesional injection into established tumours, will suppress growth of mouse mammary carcinomas (Likhite and Halpern, 1974), fibrosarcomas (Milas et a/., 1975;Woodruff and Dunbar, 1975;Suit et al, 1976), and mastocytoma (Scott, 1976), as well as mammary carcinomas in the rat (Likhite, 1974(Likhite, , 1976) and a hamster melanoma (Paslin et al, 1974). In these situations too, animals were frequently immune to further challenge with the same tumour.…”

Search for the possible role of ?immunotherapy? in operable bronchial non-small cell carcinoma (stage I and II): A phase I study with Corynebacterium parvum intrapleurally

“…CP is at least as effective as BCG in its tumour inhibiting effect in animal models (Likhite, 1976;Scott and Bomford, 1976).…”