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Dual Targeting of Tumor Cells with Bispecific Single-Chain Fv-Immunoliposomes

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Author(s): Katharina Mack | Ronny Rüger | Sina Fellermeier | Oliver Seifert | Roland E. Kontermann

Journal: Antibodies
ISSN 2073-4468

Volume: 1;
Issue: 2;
Start page: 199;
Date: 2012;
Original page

Keywords: dual targeting | bispecific immunoliposomes | single-chain Fv fragments | tumor targeting

ABSTRACT
Antibody fragments, especially single-chain Fv fragments, have been established for the generation of immunoliposomes for targeted drug delivery in cancer therapy and other applications. Bispecific immunoliposomes should be useful for dual targeting addressing inter- and intratumoral heterogeneity of tumor antigen expression. Here, we established a protocol to generate dual-targeted immunoliposomes using genetically engineered scFv molecules recognizing two different tumor-associated antigens, EGFR and CEA (CEACAM5), applying a step-wise insertion of antibody-coupled micelles into preformed PEGylated liposomes. The dual-targeted immunoliposomes retained binding activity for both antigens and combined the selectivity of both antibodies within one liposome. Thus, these dual-targeted immunoliposomes should be suitable to deliver therapeutic payloads to tumor cells expressing EGFR or CEA, or both antigens.

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