Emerging Antibody-Based HER2 (ErbB-2/neu) Therapeutics

Article type: Research Article

Authors: Krauss, W.C.^{a; b} | Park, J.W.^{a; b} | Kirpotin, D.B.^{a; b} | Hong, K.^{a; b} | Benz, C.C.^{a; b; *}

Affiliations: [a] Department of Medicine, Division of Hematology-Oncology, University of California, San Francisco, San Francisco, CA 94143, USA | [b] Liposome Research Laboratory, California Pacific Medical Center Research Institute, San Francisco, CA 94115, USA

Correspondence: [*] Corresponding author: Christopher C. Benz, M.D., Hematology-Oncology, box 1270, University of California, San Francisco, 505 Parnassus Ave., San Francisco, CA 94143-1270, USA. Tel.: +1 415 476 4149; Fax: +1 415 476 6998; E-mail: [email protected].

Abstract: Targeting HER2(ErbB-2/neu) overexpressing tumor cells to selectively deliver anticancer agents and thereby reduce host toxicity represents a rational and emerging strategy for the treatment of breast and other epithelial cancers. The extracellular domain of the HER2 receptor tyrosine kinase is readily accessible to systemically administered antibody-based therapeutics, including growth-inhibiting monclonals such as rhuMAbHER2 (trastuzmab/Herceptin©) as well as anti-HER2 immunotoxins, antibody-dependent enzyme prodrug therapy (ADEPT), and immune cell recruiting bispecific antibodies. In addition to summarizing recent advances in these antibody-based strategies, this review focuses on preclinical advances in the development of anti-HER2 immunoliposomes (ILs) as a platform technology for targeted drug delivery. Extensive in vitro and in vivo testing including efficacy and tumor uptake studies in multiple human tumor xenograft models now provide conclusive evidence for the superior therapeutic efficacy of anti-HER2 ILs-doxorubicin (dox) over free dox or liposomal (Ls)-dox, and even over combinations of dox and Ls-dox with rhuMAbHER2. As anti-HER2 ILs-dox approaches clinical testing in patients with advanced HER2 overexpressing breast cancer, future applications of this novel targeting strategy will also broaden to include intracellular delivery of other anticancer agents as well as therapeutic nucleic acids (oligonucleotides, genes).

DOI: 10.3233/BD-1999-11110

Journal: Breast Disease, vol. 11, no. 1, pp. 113-124, 1999