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Immunotherapy

PR1 peptide vaccine induces specific immunity with clinical responses in myeloid malignancies

Leukemia volume 31, pages 697–704 (2017)Cite this article

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Abstract

PR1, an HLA-A2-restricted peptide derived from both proteinase 3 and neutrophil elastase, is recognized on myeloid leukemia cells by cytotoxic T lymphocytes (CTLs) that preferentially kill leukemia and contribute to cytogenetic remission. To evaluate safety, immunogenicity and clinical activity of PR1 vaccination, a phase I/II trial was conducted. Sixty-six HLA-A2+ patients with acute myeloid leukemia (AML: 42), chronic myeloid leukemia (CML: 13) or myelodysplastic syndrome (MDS: 11) received three to six PR1 peptide vaccinations, administered subcutaneously every 3 weeks at dose levels of 0.25, 0.5 or 1.0 mg. Patients were randomized to the three dose levels after establishing the safety of the highest dose level. Primary end points were safety and immune response, assessed by doubling of PR1/HLA-A2 tetramer-specific CTL, and the secondary end point was clinical response. Immune responses were noted in 35 of 66 (53%) patients. Of the 53 evaluable patients with active disease, 12 (24%) had objective clinical responses (complete: 8; partial: 1 and hematological improvement: 3). PR1-specific immune response was seen in 9 of 25 clinical responders versus 3 of 28 clinical non-responders (P=0.03). In conclusion, PR1 peptide vaccine induces specific immunity that correlates with clinical responses, including molecular remission, in AML, CML and MDS patients.

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Acknowledgements

We thank Zhiwei He, Nancy Milam and Kathryn Quintanilla for technical assistance with the tetramer assays, detailed immunophenotyping and intracellular cytokine staining. We acknowledge Changqing Wang for his assistance with in vitro assays. We would also like to thank Dr Howard Streicher of CTEP for critical discussions of study design.

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Authors and Affiliations

  1. Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    M H Qazilbash, P F Thall, X Wang, R Rios, S Lu, S Kanodia, K E Ruisaard, J Cortes, K Clise-Dwyer, G Alatrash, Q Ma, R E Champlin & J J Molldrem

  2. Adult Stem Cell Transplant Program and Department of Medicine, University of Miami Sylvester Cancer Center, Miami, FL, USA

    E Wieder & K V Komanduri

  3. Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    S A Giralt

  4. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    E H Estey

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  1. M H Qazilbash
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  2. E Wieder
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  3. P F Thall
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  4. X Wang
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  6. S Lu
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  7. S Kanodia
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  8. K E Ruisaard
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  9. S A Giralt
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  10. E H Estey
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  11. J Cortes
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  14. G Alatrash
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  15. Q Ma
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  16. R E Champlin
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  17. J J Molldrem
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Correspondence to M H Qazilbash.

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Qazilbash, M., Wieder, E., Thall, P. et al. PR1 peptide vaccine induces specific immunity with clinical responses in myeloid malignancies. Leukemia 31, 697–704 (2017). https://doi.org/10.1038/leu.2016.254

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