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Dual Targeting of Tumor Cells with Bispecific Single-Chain Fv-Immunoliposomes
Institut für Zellbiologie und Immunologie, Universität Stuttgart, Allmandring 31, 70569 Stuttgart, Germany
Institut für Pharmazie, Friedrich-Schiller Universität Jena, Lessingstraße 8, 07743 Jena, Germany
* Author to whom correspondence should be addressed.
Received: 8 May 2012; in revised form: 9 July 2012 / Accepted: 13 July 2012 / Published: 25 July 2012
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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Mack, K.; Rüger, R.; Fellermeier, S.; Seifert, O.; Kontermann, R.E. Dual Targeting of Tumor Cells with Bispecific Single-Chain Fv-Immunoliposomes. Antibodies 2012, 1, 199-214.
Mack K, Rüger R, Fellermeier S, Seifert O, Kontermann RE. Dual Targeting of Tumor Cells with Bispecific Single-Chain Fv-Immunoliposomes. Antibodies. 2012; 1(2):199-214.
Mack, Katharina; Rüger, Ronny; Fellermeier, Sina; Seifert, Oliver; Kontermann, Roland E. 2012. "Dual Targeting of Tumor Cells with Bispecific Single-Chain Fv-Immunoliposomes." Antibodies 1, no. 2: 199-214.