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Influence of Preexisting Tumor Immunity on Bacillus Calmette-Guérin Immunotherapy of Guinea Pigs with Both Regional and Disseminated Tumor¹

Basic Research Program, National Cancer Institute Frederick Cancer Research Program, Frederick, Maryland 21701

Several clinical studies suggest that tumor immunity is present at the time of initial therapy. The purpose of this study was to modify the transplantable line 10 hepatocarcinoma model of inbred strain 2 guinea pigs so that tumor immunity would exist prior to immunotherapy. To do this, animals were given threshold doses (1 x 10⁴) line 10 cells injected intradermally. Tumors (1 cm in diameter) developed at the dermal injection site approximately 1 month later. Following surgical excision of the dermal tumors and draining nodes, animals rejected an intradermal challenge of 1 x 10⁶ line 10 cells. The strength of this tumor rejection response was positively correlated with increasing time between tumor inoculation and dermal tumor appearance. However, as this time increased, the amount of metastases in the draining lymph node also increased. When Bacillus Calmette-Guérin (BCG) was injected into 1-cm dermal tumors 22 to 41 days after tumor inoculation, 80 and 70%, respectively, of the dermal tumors regressed, while the regression of nodal metastases decreased from 70% in animals in the 22-day group (7 of 10 guinea pigs) to 29% in animals in the 41-day group (2 of 7 guinea pigs). When BCG was injected into the dermal tumor of animals that had been inoculated i.v. 24 hr earlier with 5 x 10³ line 10 cells, animals died of either pulmonary tumor or progressive tumor growth at the BCG injection site. However, if the BCG-injected tumor and draining node were excised within 5 weeks of BCG treatment, 9 of 17 guinea pigs survived, compared to 0 of 8 in the group treated with BCG alone. These results suggest that tumor burden has a greater inhibitory effect on BCG immunotherapy than does preexisting tumor immunity.

¹ Research sponsored by the National Cancer Institute under Contract NO1-CO-25423 with Litton Bionetics, Inc.

² To whom requests for reprints should be addressed, at Basic Research Program, Frederick Cancer Research Center, P.O. Box B, Frederick, Md. 21701.

Received 2/24/77. Accepted 4/28/77.