Immunotherapy in a spontaneously developed murine mammary carcinoma with syngeneic monoclonal antibody

Abstract

A new spontaneously arisen murine breast tumor, designated JC, has been established in immunocompetent BALB/c mice. Upon reestablishment of tumor in vitro and in vivo, the epithelial murine tumor cells retained their original papillary adenocarcinoma morphology. Various immunotherapy protocols have been performed in previously implanted and progressively growing JC tumor in syngeneic hosts with a murine monoclonal antibody (McAb), F36/22 (IgG3). Affinity of McAb binding to JC tumor cells was determined to be 6.1×10⁷ L/M. Quantitatively 1.2×10⁵ molecules of McAb bound to a JC tumor cell. Immunotherapeutic effectiveness in vivo on a tumor mass after its establishment is a major feature of this experimental tumor model. When four sequential administration of McAb, i.p., at a dose of 400 μg 4 days apart were used, McAb-treated animals showed statistically significant tumor regression and longer survival than those of control animals treated with an irrelevant McAb of the same isotype. Two temporal phases of tumoricidal activity were observed as measured by tumor volume reduction. The first phase of tumoricidal response (tumor regression) was detected within days upon the first administration of McAb. A distinct second phase followed within 3–5 weeks after the last McAb administration, which resulted in tumor necrosis even in large tumors. Histological examinations revealed heavy infiltration of inflammatory cells at the beginning of the second phase. Similar tumor regression was also obtained from animals treated with a single dose (400 μg) of McAb followed by injections of McAb with complete and incomplete adjuvant, respectively. These results demonstrate that this syngeneic murine mammary tumor can serve as a potential preclinical model for investigation of parameters and mechanisms associated with McAb immunotherapy.