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  • Original Article
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Immunology

Clinical evaluation of BCR-ABL peptide immunisation in chronic myeloid leukaemia: results of the EPIC study

Abstract

Peptides from the e14a2 BCR-ABL junction will elicit T-cell responses in vitro. Here, 19 imatinib treated CML patients in first chronic phase were vaccinated with BCR-ABL peptides spanning the e14a2 fusion junction, some of which were linked to the pan DR epitope PADRE to augment CD4+ T cell help. Six vaccinations were given over 9 weeks, together with sargramostim. All patients developed mild local reactions. T cell responses to PADRE were seen in all patients. Fourteen of 19 patients developed T cell responses to BCR-ABL peptides. The development of an anti-BCR-ABL T cell response correlated with a subsequent fall in BCR-ABL transcripts. No molecular benefit was seen in the 5 patients not in major cytogenetic response (MCR) at baseline. However, of the 14 patients in MCR at baseline, 13 developed at least 1 log fall in BCR-ABL transcripts, though this occurred several months after completing vaccination, consistent with an effect at a primitive CML stem cell level. Vaccination may improve the fall in BCR-ABL transcripts in patients who have received imatinib for more than 12 months. BCR-ABL peptide vaccination may improve control of CML, especially in patients responding well to imatinib. Randomised trials are required to address this further.

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Acknowledgements

The authors are grateful to Dr Paul Travers of the Anthony Nolan Research Centre (London) for early discussion on the design of the study. The study was supported by a clinical research grant from the Leukaemia Research Fund of Great Britain. JMR and LW designed and carried out the immunological and molecular assessments respectively; KK was in day to day clinical charge of the study; REC conceived the study, was responsible for regulatory issues and overall clinical charge and wrote the manuscript.

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Correspondence to R E Clark.

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Rojas, J., Knight, K., Wang, L. et al. Clinical evaluation of BCR-ABL peptide immunisation in chronic myeloid leukaemia: results of the EPIC study. Leukemia 21, 2287–2295 (2007). https://doi.org/10.1038/sj.leu.2404858

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