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Influence of Immunotherapeutic Agents on the Progression of Spontaneously Arising, Metastasizing Rat Mammary Adenocarcinomas of Varying Immunogenicities¹

Cancer Research Campaign Laboratories, University of Nottingham, University Park, Nottingham, NG7 2RD, England

One hundred ninety-six Nottingham Wistar (Not-W) rats were inoculated in the mammary pad tissue with tumor cells from one of three spontaneously arising rat mammary adenocarcinomas of discrete immunogenicities. Animals were treated with multiple intratumoral or i.v. injections of either Corynebacterium parvum suspension (CP) or Bacillus Calmette-Guérin vaccine (BCG). Animals inoculated with cells from the most immunogenic tumor line were with a spectrum of immunotherapeutic responses. The most significant results were found in animals treated with multiple intratumoral injections of CP. In this group all of the primary tumors regressed, and regional lymph nodes were protected from the formation of gross metastases. Intratumoral BCG was found to be effective only against primary tumor growth. Either agent regressed appropriately sized regional lymph node metastases if injected directly into the metastatic tumor. Early initiated i.v. CP or BCG significantly reduced the incidence of regional lymph node metastases when excision of primary tumors was performed prior to the termination of immunotherapy. However, late i.v. immunotherapy, begun when regional lymph nodes were already palpable, did not alter the incidence of regional lymph node metastases. Successfully treated animals were found to have over 1000-fold increased resistance to rechallenge with the most immunogenic tumor cells but not to cells from a less immunogenic tumor line. Finally, the identical immunotherapeutic regimens were ineffective in the control of tumor progression in animals bearing the less immunogenic tumors.

It is concluded that CP and BCG are effective immunotherapeutic agents when utilized in early stages of disease against appropriate animal tumors.

¹ This research was supported by USPHS Training Grant 5 T01 GM01930-08 from the NIH and by a departmental grant from the Cancer Research Campaign.

² To whom requests for reprints should be addressed.

Received 7/20/77. Accepted 10/12/77.