Phage idiotype vaccination: first phase I/II clinical trial in patients with multiple myeloma

Journal of Translational Medicine

Fuat S Oduncu⁶  Carole Bourquin³  Michael Flaig¹  Thomas Böhm⁶  Mariel Donzeau⁴  Todd Braciak⁶  Christina Blumenthal⁶  Wolfgang Nagel⁵  Cornelia Then²  Tim Roehnisch⁶ 

[1] Dermatologische Klinik der Universität München, Munich, Germany;Division of Endocrinology and Diabetology, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany;Université de Fribourg, Département de Médecine, Chair of Pharmacology, Fribourg, Switzerland;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;Division of Hematology and Oncology, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany

关键词: Paraprotein;    Phase I/II clinical trial;    Multiple myeloma;    Phage idiotype vaccination;    Patient-specific immunotherapy;   

Others  :  814071
DOI  :  10.1186/1479-5876-12-119

 received in 2014-02-13, accepted in 2014-04-29,  发布年份 2014

【 摘 要 】

Background

Multiple myeloma is characterized by clonal expansion of B cells producing monoclonal immunoglobulins or fragments thereof, which can be detected in the serum and/or urine and are ideal target antigens for patient-specific immunotherapies.

Methods

Using phage particles as immunological carriers, we employed a novel chemically linked idiotype vaccine in a clinical phase I/II trial including 15 patients with advanced multiple myeloma. Vaccines composed of purified paraproteins linked to phage were manufactured successfully for each patient. Patients received six intradermal immunizations with phage idiotype vaccines in three different dose groups.

Results

Phage idiotype was well tolerated by all study participants. A subset of patients (80% in the middle dose group) displayed a clinical response indicated by decrease or stabilization of paraprotein levels. Patients exhibiting a clinical response to phage vaccines also raised idiotype-specific immunoglobulins. Induction of a cellular immune response was demonstrated by a cytotoxicity assay and delayed type hypersensitivity tests.

Conclusion

We present a simple, time- and cost-efficient phage idiotype vaccination strategy, which represents a safe and feasible patient-specific therapy for patients with advanced multiple myeloma and produced promising anti-tumor activity in a subset of patients.

【 授权许可】

   
2014 Roehnisch et al.; licensee BioMed Central Ltd.

【 图 表 】

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