Chemically linked phage idiotype vaccination in the murine B cell lymphoma 1 model

Journal of Translational Medicine

Fuat Oduncu³  Carole Bourquin¹  Thomas Böhm³  Mariel Donzeau⁴  Todd Braciak³  Christina Blumenthal³  Wolfgang Nagel⁵  Cornelia Then²  Tim Roehnisch³ 

[1] Département de Médecine, Chair of Pharmacology, Université de Fribourg, Fribourg, Switzerland;Division of Endocrinology and Diabetology, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany;Division of Hematology and Oncology, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ziemssenstrasse 1, D-80336, Munich, Germany;Maître de conférences (MCF), Université de Strasbourg, Unité UMR Biotechnologie et Signalisation Cellulaire, Strasbourg, France;Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt, Munich, Germany

关键词: KLH;    Murine BCL1 lymphoma model;    B cell lymphoma;    Phage idiotype vaccination;   

Others  :  824900
DOI  :  10.1186/1479-5876-11-267

 received in 2013-08-24, accepted in 2013-10-07,  发布年份 2013

【 摘 要 】

Background

B cell malignancies are characterized by clonal expansion of B cells expressing tumor-specific idiotypes on their surface. These idiotypes are ideal target antigens for an individualized immunotherapy. However, previous idiotype vaccines mostly lacked efficiency due to a low immunogenicity of the idiotype. The objective of the present study was the determination of the feasibility, safety and immunogenicity of a novel chemically linked phage idiotype vaccine.

Methods

In the murine B cell lymphoma 1 model, tumor idiotypes were chemically linked to phage particles used as immunological carriers. For comparison, the idiotype was genetically expressed on the major phage coat protein g8 or linked to keyhole limpet hemocynanin. After intradermal immunizations with idiotype vaccines, tolerability and humoral immune responses were assessed.

Results

Feasibility and tolerability of the chemically linked phage idiotype vaccine was demonstrated. Vaccination with B cell lymphoma 1 idiotype expressing phage resulted in a significant survival benefit in the murine B cell lymphoma 1 protection model (60.2 ± 23.8 days vs. 41.8 ± 1.6 days and 39.8 ± 3.8 days after vaccination with wild type phage or phosphate buffered saline, respectively). Superior immunogenicity of the chemically linked phage idiotype vaccine compared to the genetically engineered phage idiotype and keyhole limpet hemocynanin-coupled idiotype vaccine was demonstrated by significantly higher B cell lymphoma 1 idiotype-specific IgG levels after vaccination with chemically linked phage idiotype.

Conclusion

We present a novel, simple, time- and cost-efficient phage idiotype vaccination strategy, which represents a safe and feasible therapy and may produce a superior immune response compared to previously employed idiotype vaccination strategies.

【 授权许可】

   
2013 Roehnisch et al.; licensee BioMed Central Ltd.

【 图 表 】

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