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01-09-2007 | Original Article

Development of anti-PAX3 immune responses; a target for cancer immunotherapy

Authors: Nourredine Himoudi, Steven Nabarro, Mengyong Yan, Kimberly Gilmour, Adrian J. Thrasher, John Anderson

Published in: Cancer Immunology, Immunotherapy | Issue 9/2007

Abstract

PAX3 is overexpressed in several human cancers and is absent from normal adult human tissues. It is known to have an oncogenic function in human malignancy, and is therefore a promising target for cancer immunotherapy. We screened the murine and human PAX3 amino acid sequences for peptides that bind common MHC class I types, and identified murine GVFINGRPL and human KLTEARVQV sequences. Mice immunised with either a selected PAX3 peptide, or with a PAX3 expressing DNA vector, developed specific anti-PAX3 immune responses that inhibited tumour growth. The intensity of the immune response was significantly enhanced by pulsing of the peptide onto dendritic cells. Anti-PAX3 T cell lines were established from splenocytes of immunised mice. Intravenous administration of anti-PAX3 T cells caused regression of established tumours indicating a promising clinical application for anti-PAX3 immunotherapy. The human peptide stimulated growth of similar T cell lines from peripheral blood of three out of three normal human blood donors. These showed specific cytotoxicity against a range of human PAX3+ and HLA-A2+ cancer cell lines. Moreover, an anti-PAX3 response was detected as a component of the anti-tumour immune response in a patient treated with lysate pulsed dendritic cell vaccination. The ability to generate strong and specific anti PAX3 immune responses from the T cell repertoire in both mice and humans, provides evidence for PAX3 as a promising target for immunotherapy of cancer.

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Title: Development of anti-PAX3 immune responses; a target for cancer immunotherapy
Authors: Nourredine Himoudi
Steven Nabarro
Mengyong Yan
Kimberly Gilmour
Adrian J. Thrasher
John Anderson
Publication date: 01-09-2007
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 9/2007
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-007-0294-3

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