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

M. H. Qazilbash, E. Wieder, P. F. Thall, X. Wang, R. Rios, S. Lu, S. Kanodia, K. E. Ruisaard, S. A. Giralt, E. H. Estey, J. Cortes, K. V. Komanduri, K. Clise-Dwyer, G. Alatrash, Q. Ma, R. E. Champlin, J. J. Molldrem

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)697-704
Number of pages8
JournalLeukemia
Volume31
Issue number3
DOIs
StatePublished - Mar 1 2017
Externally publishedYes

Fingerprint

Subunit Vaccines
Immunity
HLA-A2 Antigen
Cytotoxic T-Lymphocytes
Neoplasms
Safety
Vaccination
Myeloblastin
Leukocyte Elastase
Peptides
Myeloid Leukemia
Myelodysplastic Syndromes
Myeloid Cells
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Acute Myeloid Leukemia
Cytogenetics
Leukemia

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Qazilbash, M. H., Wieder, E., Thall, P. F., Wang, X., Rios, R., Lu, S., ... Molldrem, J. J. (2017). PR1 peptide vaccine induces specific immunity with clinical responses in myeloid malignancies. Leukemia, 31(3), 697-704. https://doi.org/10.1038/leu.2016.254

PR1 peptide vaccine induces specific immunity with clinical responses in myeloid malignancies. / Qazilbash, M. H.; Wieder, E.; Thall, P. F.; Wang, X.; Rios, R.; Lu, S.; Kanodia, S.; Ruisaard, K. E.; Giralt, S. A.; Estey, E. H.; Cortes, J.; Komanduri, K. V.; Clise-Dwyer, K.; Alatrash, G.; Ma, Q.; Champlin, R. E.; Molldrem, J. J.

In: Leukemia, Vol. 31, No. 3, 01.03.2017, p. 697-704.

Research output: Contribution to journalArticle

Qazilbash, MH, Wieder, E, Thall, PF, Wang, X, Rios, R, Lu, S, Kanodia, S, Ruisaard, KE, Giralt, SA, Estey, EH, Cortes, J, Komanduri, KV, Clise-Dwyer, K, Alatrash, G, Ma, Q, Champlin, RE & Molldrem, JJ 2017, 'PR1 peptide vaccine induces specific immunity with clinical responses in myeloid malignancies', Leukemia, vol. 31, no. 3, pp. 697-704. https://doi.org/10.1038/leu.2016.254
Qazilbash MH, Wieder E, Thall PF, Wang X, Rios R, Lu S et al. PR1 peptide vaccine induces specific immunity with clinical responses in myeloid malignancies. Leukemia. 2017 Mar 1;31(3):697-704. https://doi.org/10.1038/leu.2016.254
Qazilbash, M. H. ; Wieder, E. ; Thall, P. F. ; Wang, X. ; Rios, R. ; Lu, S. ; Kanodia, S. ; Ruisaard, K. E. ; Giralt, S. A. ; Estey, E. H. ; Cortes, J. ; Komanduri, K. V. ; Clise-Dwyer, K. ; Alatrash, G. ; Ma, Q. ; Champlin, R. E. ; Molldrem, J. J. / PR1 peptide vaccine induces specific immunity with clinical responses in myeloid malignancies. In: Leukemia. 2017 ; Vol. 31, No. 3. pp. 697-704.
@article{83408a9677ef42f9a4f4f79d846d9fec,
title = "PR1 peptide vaccine induces specific immunity with clinical responses in myeloid malignancies",
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.",
author = "Qazilbash, {M. H.} and E. Wieder and Thall, {P. F.} and X. Wang and R. Rios and S. Lu and S. Kanodia and Ruisaard, {K. E.} and Giralt, {S. A.} and Estey, {E. H.} and J. Cortes and Komanduri, {K. V.} and K. Clise-Dwyer and G. Alatrash and Q. Ma and Champlin, {R. E.} and Molldrem, {J. J.}",
year = "2017",
month = "3",
day = "1",
doi = "10.1038/leu.2016.254",
language = "English (US)",
volume = "31",
pages = "697--704",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - PR1 peptide vaccine induces specific immunity with clinical responses in myeloid malignancies

AU - Qazilbash, M. H.

AU - Wieder, E.

AU - Thall, P. F.

AU - Wang, X.

AU - Rios, R.

AU - Lu, S.

AU - Kanodia, S.

AU - Ruisaard, K. E.

AU - Giralt, S. A.

AU - Estey, E. H.

AU - Cortes, J.

AU - Komanduri, K. V.

AU - Clise-Dwyer, K.

AU - Alatrash, G.

AU - Ma, Q.

AU - Champlin, R. E.

AU - Molldrem, J. J.

PY - 2017/3/1

Y1 - 2017/3/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84991736511&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84991736511&partnerID=8YFLogxK

U2 - 10.1038/leu.2016.254

DO - 10.1038/leu.2016.254

M3 - Article

C2 - 27654852

AN - SCOPUS:84991736511

VL - 31

SP - 697

EP - 704

JO - Leukemia

JF - Leukemia

SN - 0887-6924

IS - 3

ER -