25. Juli 2012

Mack & al., accepted in Antibodies

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

Accepted for publication in Antibodies:

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


Katharina Mack 1 , Ronny Rüger 2 , Sina Fellermeier 1 , Oliver Seifert 1 and Roland E. Kontermann 1,*

1 Institut für Zellbiologie und Immunologie; Universität Stuttgart; Stuttgart, Germany
2 Institut für Pharmazie, Friedrich-Schiller Universität Jena, Lessingstraße 8, 07743 Jena, Germany
* Author to whom correspondence should be addressed

 

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.

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

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