An Experimental Model for the Immunological Treatment of Breast Cancer

Abstract

A mixture (“cocktail”) of four anti-breast epithelial monoclonal antibodies was injected into nude mice carrying a transplantable human mammary tumor. Two model systems were developed to test the capability of these monoclonal antibodies to arrest human mammary tumor growth. In the first approach the ability of these monoclonal antibodies to arrest metastatic dissemination was tried by injection of these monoclonal antibodies prior to tumor implantation (“passive immunization”). In the second approach the action of monoclonal antibodies on established and growing breast tumors was tested. In the former case of passive immunization treatment, human mammary tumors in nude mice were arrested completely in their growth or to one-tenth the size of controls when injected with a mixture of all of these breast specific monoclonal antibodies and to a lesser extent with single monoclonal antibodies or incomplete mixtures were used. Other human carcinomas under the same protocol were not affected. In the second case, of injection into established tumors, in every opportunity tested a very large and significant arrest of growth was obtained.

It has been established that tumors are heterogenous in expression of breast epithelial antigens recognized by our antibodies to the extent that some cells may have no detectable amount of a particular antigen. The breast tumor mass that did grow in the passive immunization studies after 8 weeks in the nude mice injected with the cocktail of monoclonal antibodies revealed a considerable reduction in antigen content recognized by these anti-breast epithelial monoclonal antibodies when compared to untreated tumors.

These results attest to the effectiveness of unconjugated anti-breast monoclonal antibodies to arrest human breast tumor growth in nude mice and they also suggest that to best arrest tumor growth a mixture of monoclonal antibodies should be applied.