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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 2/2011

Open Access 01-02-2011 | Original Article

Pitfalls of vaccinations with WT1-, Proteinase3- and MUC1-derived peptides in combination with MontanideISA51 and CpG7909

Authors: Jürgen Kuball, Karin de Boer, Eva Wagner, Mohammed Wattad, Edite Antunes, Risini D. Weeratna, Alain P. Vicari, Carina Lotz, Suzanne van Dorp, Samantha Hol, Philip D. Greenberg, Wolfgang Heit, Heather L. Davis, Matthias Theobald

Published in: Cancer Immunology, Immunotherapy | Issue 2/2011

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Abstract

T cells with specificity for antigens derived from Wilms Tumor gene (WT1), Proteinase3 (Pr3), and mucin1 (MUC1) have been demonstrated to lyse acute myeloid leukemia (AML) blasts and multiple-myeloma (MM) cells, and strategies to enhance or induce such tumor-specific T cells by vaccination are currently being explored in multiple clinical trials. To test safety and immunogenicity of a vaccine composed of WT1-, Pr3-, and MUC1-derived Class I-restricted peptides and the pan HLA-DR T helper cell epitope (PADRE) or MUC1-helper epitopes in combination with CpG7909 and MontanideISA51, four patients with AML and five with MM were repetitively vaccinated. No clinical responses were observed. Neither pre-existing nor naive WT1-/Pr3-/MUC1-specific CD8+ T cells expanded in vivo by vaccination. In contrast, a significant decline in vaccine-specific CD8+ T cells was observed. An increase in PADRE-specific CD4+ T helper cells was observed after vaccination but these appeared unable to produce IL2, and CD4+ T cells with a regulatory phenotype increased. Taken into considerations that multiple clinical trials with identical antigens but different adjuvants induced vaccine-specific T cell responses, our data caution that a vaccination with leukemia-associated antigens can be detrimental when combined with MontanideISA51 and CpG7909. Reflecting the time-consuming efforts of clinical trials and the fact that 1/3 of ongoing peptide vaccination trails use CpG and/or Montanide, our data need to be taken into consideration.

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Metadata
Title
Pitfalls of vaccinations with WT1-, Proteinase3- and MUC1-derived peptides in combination with MontanideISA51 and CpG7909
Authors
Jürgen Kuball
Karin de Boer
Eva Wagner
Mohammed Wattad
Edite Antunes
Risini D. Weeratna
Alain P. Vicari
Carina Lotz
Suzanne van Dorp
Samantha Hol
Philip D. Greenberg
Wolfgang Heit
Heather L. Davis
Matthias Theobald
Publication date
01-02-2011
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 2/2011
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-010-0929-7

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