RT Journal Article SR Electronic T1 Regression of Established Breast Carcinoma Xenografts with Antibody-directed Enzyme Prodrug Therapy against c-erbB2 p185 JF Cancer Research JO Cancer Res FD American Association for Cancer Research SP 5171 OP 5177 VO 54 IS 19 A1 Eccles, Suzanne A. A1 Court, William J. A1 Box, Gary A. A1 Dean, Christopher J. A1 Melton, Roger G. A1 Springer, Caroline J. YR 1994 UL http://cancerres.aacrjournals.org/content/54/19/5171.abstract AB The enzyme carboxypeptidase G2 (CPG2) was conjugated to the rat IgG2a monoclonal antibody (mAb) ICR12, which recognizes the external domain of the human c-erbB2 protooncogene product. The conjugate retained antigen-binding and enzyme activity. Radiolabeled conjugate localized efficiently and stably to MDA MB 361 breast carcinoma xenografts, which overexpress the c-erbB2 gene product p185. Radiotracer determinations and plasma enzyme activity studies in nu/nu mice gave conjugate blood clearance rate half-lives of approximately 4 days. In separate antibody-directed enzyme prodrug therapy regimes, one dose of the 4-[(2-chloroethyl)(2-mesyloxyethyl)amino]benzoyl-l-glutamic acid prodrug was administered to nu/nu mice bearing established MDA MB 361 tumors (mean volume, 170–260 mm3). In mice which had received ICR12-CPG2 12–14 days previously, sustained dose-dependent tumor stasis or regressions were effected, which in some cases persisted throughout observation periods of up to 90 days. In control mice which had received the isotype-matched irrelevant mAb ICR16-CPG2 conjugate, tumors grew progressively, as did those in mice treated with prodrug alone, or treated simultaneously with ICR12-CPG2 and prodrug at the maximum tolerated dose. Control chemotherapy with conventional drugs proved toxic and induced only minimal growth delays. ©1994 American Association for Cancer Research.