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Research Articles: Therapeutics, Targets, and Development

Anti-CD166 single chain antibody-mediated intracellular delivery of liposomal drugs to prostate cancer cells

Departments of ¹ Anesthesia and ² Pharmaceutical Chemistry, University of California at San Francisco; ³ University of California San Francisco Comprehensive Cancer Center, San Francisco, California; ⁴ Hermes Biosciences, Inc., South San Francisco, California; and ⁵ Buck Institute for Age Research, Novato, California

Requests for reprints: Bin Liu, Department of Anesthesia, University of California at San Francisco, Room 3C38, 1001 Potrero Avenue, San Francisco, CA 94110. Phone: 415-206-6973; Fax: 415-206-6276. E-mail: liub{at}anesthesia.ucsf.edu

Abstract

Targeted delivery of small-molecule drugs has the potential to enhance selective killing of tumor cells. We have identified previously an internalizing single chain [single chain variable fragment (scFv)] antibody that targets prostate cancer cells and identified the target antigen as CD166. We report here the development of immunoliposomes using this anti-CD166 scFv (H3). We studied the effects of a panel of intracellularly delivered, anti-CD166 immunoliposomal small-molecule drugs on prostate cancer cells. Immunoliposomal formulations of topotecan, vinorelbine, and doxorubicin each showed efficient and targeted uptake by three prostate cancer cell lines (Du-145, PC3, and LNCaP). H3-immunoliposomal topotecan was the most effective in cytotoxicity assays on all three tumor cell lines, showing improved cytotoxic activity compared with nontargeted liposomal topotecan. Other drugs such as liposomal doxorubicin were highly effective against LNCaP but not PC3 or Du-145 cells, despite efficient intracellular delivery. Post-internalization events thus modulate the overall efficacy of intracellulary delivered liposomal drugs, contributing in some cases to the lower than expected activity in a cell line–dependent manner. Further studies on intracellular tracking of endocytosed liposomal drugs will help identify and overcome the barriers limiting the potency of liposomal drugs. [Mol Cancer Ther 2007;6(10):2737–46]

Grant support: National Cancer Institute/NIH grants P50 CA89520 and R01 CA118919.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

⁶ Supplementary material for this article is available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/).

Received 2/28/07; revised 6/15/07; accepted 8/ 8/07.

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