NY-ESO-1 vaccination in combination with decitabine induces antigen-specific T-lymphocyte responses in patients with myelodysplastic syndrome

Elizabeth A. Griffiths, Pragya Srivastava, Junko Matsuzaki, Zachary Brumberger, Eunice S. Wang, Justin Kocent, Austin Miller, Gregory W. Roloff, Hong Yuen Wong, Benjamin E. Paluch, Linda G. Lutgen-Dunckley, Brandon L. Martens, Kunle Odunsi, Adam R Karpf, Christopher S. Hourigan, Michael J. Nemeth

Research output: Contribution to journalArticle

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Abstract

Purpose: Treatment options are limited for patients with high-risk myelodysplastic syndrome (MDS). The azanucleosides, azacitidine and decitabine, are first-line therapy for MDS that induce promoter demethylation and gene expression of the highly immunogenic tumor antigen NY-ESO-1. We demonstrated that patients with acute myeloid leukemia (AML) receiving decitabine exhibit induction of NY-ESO-1 expression in circulating blasts. We hypothesized that vaccinating against NY-ESO-1 in patients with MDS receiving decitabine would capitalize upon induced NY-ESO-1 expression in malignant myeloid cells to provoke an NY-ESO-1–specific MDS-directed cytotoxic T-cell immune response. Experimental Design: In a phase I study, 9 patients with MDS received an HLA-unrestricted NY-ESO-1 vaccine (CDX-1401 þ poly-ICLC) in a nonoverlapping schedule every four weeks with standard-dose decitabine. Results: Analysis of samples serially obtained from the 7 patients who reached the end of the study demonstrated induction of NY-ESO-1 expression in 7 of 7 patients and NY-ESO-1–specific CD4 þ and CD8 þ T-lymphocyte responses in 6 of 7 and 4 of 7 of the vaccinated patients, respectively. Myeloid cells expressing NY-ESO-1, isolated from a patient at different time points during decitabine therapy, were capable of activating a cytotoxic response from autologous NY-ESO-1–specific T lymphocytes. Vaccine responses were associated with a detectable population of CD141 Hi conventional dendritic cells, which are critical for the uptake of NY-ESO-1 vaccine and have a recognized role in antitumor immune responses. Conclusions: These data indicate that vaccination against induced NY-ESO-1 expression can produce an antigen-specific immune response in a relatively nonimmunogenic myeloid cancer and highlight the potential for induced antigen-directed immunotherapy in a group of patients with limited options.

Original languageEnglish (US)
Pages (from-to)1019-1029
Number of pages11
JournalClinical Cancer Research
Volume24
Issue number5
DOIs
StatePublished - Mar 1 2018

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decitabine
Myelodysplastic Syndromes
Vaccination
T-Lymphocytes
Antigens
Vaccines
Myeloid Cells
Azacitidine
Histocompatibility Antigens Class II
Neoplasm Antigens

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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NY-ESO-1 vaccination in combination with decitabine induces antigen-specific T-lymphocyte responses in patients with myelodysplastic syndrome. / Griffiths, Elizabeth A.; Srivastava, Pragya; Matsuzaki, Junko; Brumberger, Zachary; Wang, Eunice S.; Kocent, Justin; Miller, Austin; Roloff, Gregory W.; Wong, Hong Yuen; Paluch, Benjamin E.; Lutgen-Dunckley, Linda G.; Martens, Brandon L.; Odunsi, Kunle; Karpf, Adam R; Hourigan, Christopher S.; Nemeth, Michael J.

In: Clinical Cancer Research, Vol. 24, No. 5, 01.03.2018, p. 1019-1029.

Research output: Contribution to journalArticle

Griffiths, EA, Srivastava, P, Matsuzaki, J, Brumberger, Z, Wang, ES, Kocent, J, Miller, A, Roloff, GW, Wong, HY, Paluch, BE, Lutgen-Dunckley, LG, Martens, BL, Odunsi, K, Karpf, AR, Hourigan, CS & Nemeth, MJ 2018, 'NY-ESO-1 vaccination in combination with decitabine induces antigen-specific T-lymphocyte responses in patients with myelodysplastic syndrome', Clinical Cancer Research, vol. 24, no. 5, pp. 1019-1029. https://doi.org/10.1158/1078-0432.CCR-17-1792
Griffiths, Elizabeth A. ; Srivastava, Pragya ; Matsuzaki, Junko ; Brumberger, Zachary ; Wang, Eunice S. ; Kocent, Justin ; Miller, Austin ; Roloff, Gregory W. ; Wong, Hong Yuen ; Paluch, Benjamin E. ; Lutgen-Dunckley, Linda G. ; Martens, Brandon L. ; Odunsi, Kunle ; Karpf, Adam R ; Hourigan, Christopher S. ; Nemeth, Michael J. / NY-ESO-1 vaccination in combination with decitabine induces antigen-specific T-lymphocyte responses in patients with myelodysplastic syndrome. In: Clinical Cancer Research. 2018 ; Vol. 24, No. 5. pp. 1019-1029.
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abstract = "Purpose: Treatment options are limited for patients with high-risk myelodysplastic syndrome (MDS). The azanucleosides, azacitidine and decitabine, are first-line therapy for MDS that induce promoter demethylation and gene expression of the highly immunogenic tumor antigen NY-ESO-1. We demonstrated that patients with acute myeloid leukemia (AML) receiving decitabine exhibit induction of NY-ESO-1 expression in circulating blasts. We hypothesized that vaccinating against NY-ESO-1 in patients with MDS receiving decitabine would capitalize upon induced NY-ESO-1 expression in malignant myeloid cells to provoke an NY-ESO-1–specific MDS-directed cytotoxic T-cell immune response. Experimental Design: In a phase I study, 9 patients with MDS received an HLA-unrestricted NY-ESO-1 vaccine (CDX-1401 {\th} poly-ICLC) in a nonoverlapping schedule every four weeks with standard-dose decitabine. Results: Analysis of samples serially obtained from the 7 patients who reached the end of the study demonstrated induction of NY-ESO-1 expression in 7 of 7 patients and NY-ESO-1–specific CD4 {\th} and CD8 {\th} T-lymphocyte responses in 6 of 7 and 4 of 7 of the vaccinated patients, respectively. Myeloid cells expressing NY-ESO-1, isolated from a patient at different time points during decitabine therapy, were capable of activating a cytotoxic response from autologous NY-ESO-1–specific T lymphocytes. Vaccine responses were associated with a detectable population of CD141 Hi conventional dendritic cells, which are critical for the uptake of NY-ESO-1 vaccine and have a recognized role in antitumor immune responses. Conclusions: These data indicate that vaccination against induced NY-ESO-1 expression can produce an antigen-specific immune response in a relatively nonimmunogenic myeloid cancer and highlight the potential for induced antigen-directed immunotherapy in a group of patients with limited options.",
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T1 - NY-ESO-1 vaccination in combination with decitabine induces antigen-specific T-lymphocyte responses in patients with myelodysplastic syndrome

AU - Griffiths, Elizabeth A.

AU - Srivastava, Pragya

AU - Matsuzaki, Junko

AU - Brumberger, Zachary

AU - Wang, Eunice S.

AU - Kocent, Justin

AU - Miller, Austin

AU - Roloff, Gregory W.

AU - Wong, Hong Yuen

AU - Paluch, Benjamin E.

AU - Lutgen-Dunckley, Linda G.

AU - Martens, Brandon L.

AU - Odunsi, Kunle

AU - Karpf, Adam R

AU - Hourigan, Christopher S.

AU - Nemeth, Michael J.

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Purpose: Treatment options are limited for patients with high-risk myelodysplastic syndrome (MDS). The azanucleosides, azacitidine and decitabine, are first-line therapy for MDS that induce promoter demethylation and gene expression of the highly immunogenic tumor antigen NY-ESO-1. We demonstrated that patients with acute myeloid leukemia (AML) receiving decitabine exhibit induction of NY-ESO-1 expression in circulating blasts. We hypothesized that vaccinating against NY-ESO-1 in patients with MDS receiving decitabine would capitalize upon induced NY-ESO-1 expression in malignant myeloid cells to provoke an NY-ESO-1–specific MDS-directed cytotoxic T-cell immune response. Experimental Design: In a phase I study, 9 patients with MDS received an HLA-unrestricted NY-ESO-1 vaccine (CDX-1401 þ poly-ICLC) in a nonoverlapping schedule every four weeks with standard-dose decitabine. Results: Analysis of samples serially obtained from the 7 patients who reached the end of the study demonstrated induction of NY-ESO-1 expression in 7 of 7 patients and NY-ESO-1–specific CD4 þ and CD8 þ T-lymphocyte responses in 6 of 7 and 4 of 7 of the vaccinated patients, respectively. Myeloid cells expressing NY-ESO-1, isolated from a patient at different time points during decitabine therapy, were capable of activating a cytotoxic response from autologous NY-ESO-1–specific T lymphocytes. Vaccine responses were associated with a detectable population of CD141 Hi conventional dendritic cells, which are critical for the uptake of NY-ESO-1 vaccine and have a recognized role in antitumor immune responses. Conclusions: These data indicate that vaccination against induced NY-ESO-1 expression can produce an antigen-specific immune response in a relatively nonimmunogenic myeloid cancer and highlight the potential for induced antigen-directed immunotherapy in a group of patients with limited options.

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