PT  - JOURNAL ARTICLE
AU  - Eccles, Suzanne A.
AU  - Court, William J.
AU  - Box, Gary A.
AU  - Dean, Christopher J.
AU  - Melton, Roger G.
AU  - Springer, Caroline J.
TI  - Regression of Established Breast Carcinoma Xenografts with Antibody-directed Enzyme Prodrug Therapy against c-<em>erb</em>B2 p185
DP  - 1994 Oct 01
TA  - Cancer Research
PG  - 5171--5177
VI  - 54
IP  - 19
4099  - http://cancerres.aacrjournals.org/content/54/19/5171.short
4100  - http://cancerres.aacrjournals.org/content/54/19/5171.full
SO  - Cancer Res1994 Oct 01; 54
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.