INDUCTION OF HUMAN BREAST CANCER-SPECIFIC ANTIBODY-RESPONSES IN CYNOMOLGUS MONKEYS BY A MURINE MONOCLONAL ANTIIDIOTYPE ANTIBODY

We have generated and characterized a murine monoclonal anti-idiotype (Id) antibody, designated 11D10, which biologically and antigenically mimics a distinct and specific epitope of the high molecular weight hu man milk fat globule primarily expressed by human breast and some othe r tumor cells at high density. This epitope is identified by mAb BrE1, which was used as the immunizing antibody or Ab1 to generate the anti -Id (Ab2) 11D10. 11D10 induced antitumor immune responses across speci es barriers, i.e., in mice and rabbits. In preclinical studies, cynomo lgus monkeys were immunized with 2 mg of either 11D10 or the isotype- and allotype-matched control Ab2 3H1 after precipitation with aluminum hydroxide. All monkeys developed high titers of antibodies against th e immunizing mouse immunoglobulin. Immunization with 11D10 induced ant i-anti-idiotype antibodies (Ab3) which reacted with breast cancer cell lines but not with control T-cell and melanoma cell lines. The Ab3 sh ared idiotypes with BrE1 (Ab1), as demonstrated by their ability to in hibit 11D10 binding to BrE1. The Ab3 obtained with 11D10 bound specifi cally to human milk fat globule antigen and competed with BrE1 for bin ding to breast cancer cell lines, suggesting that Ab1 and Ab3 may bind to the same epitope. In addition, Id-specific cellular immune respons es were demonstrated in monkeys immunized with 11D10 by T-cell prolife ration assays. These results indicate that aluminum hydroxide-precipit ated anti-Id 11D10 fan induce breast canter-specific antibodies in non human primates and can serve as a potential network antigen for breast cancer patients.