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Induction of Human Breast Cancer-specific Antibody Responses in Cynomolgus Monkeys by a Murine Monoclonal Anti-Idiotype Antibody¹

The Lucille Parker Markey Cancer Center and the Departments of Microbiology and Immunology [M. C., H. K., and M. B-C.] and Internal Medicine [K. A. F.], University of Kentucky Medical Center, Lexington, Kentucky 40536; and the Cancer Research Fund of Contra Costa, Walnut Creek, California 94596 [R.L.C.]

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 human milk fat globule primarily expressed by human breast and some other 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 species barriers, i.e., in mice and rabbits. In preclinical studies, cynomolgus 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 the immunizing mouse immunoglobulin. Immunization with 11D10 induced anti-anti-idiotype antibodies (Ab3) which reacted with breast cancer cell lines but not with control T-cell and melanoma cell lines. The Ab3 shared idiotypes with BrE1 (Ab1), as demonstrated by their ability to inhibit 11D10 binding to BrE1. The Ab3 obtained with 11D10 bound specifically to human milk fat globule antigen and competed with BrE1 for binding to breast cancer cell lines, suggesting that Ab1 and Ab3 may bind to the same epitope. In addition, Id-specific cellular immune responses were demonstrated in monkeys immunized with 11D10 by T-cell proliferation assays. These results indicate that aluminum hydroxide-precipitated anti-Id 11D10 can induce breast cancer-specific antibodies in nonhuman primates and can serve as a potential network antigen for breast cancer patients.

¹ This work was supported in part by NIH Grants CA 47860 and CA 57165. Presented at the Mini-Symposium, AACR Annual Meeting, April 10–13, 1994, San Francisco, California. Presenter, Mala Chakraborty, received the Bristol Meyer Travel Award for the abstract.

² Present address: Cancer Immunobiology Laboratory, 35 Billfries Drive, Building F, Hilton Head Island, SC 29925.

³ To whom requests for reprints should be addressed, at the Markey Cancer Center, 207 Combs Cancer Research Building, 800 Rose Street, Lexington, KY 40536-0096.

Received 10/24/94. Accepted 1/25/95.

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