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NY-ESO-1 Vaccination in Combination with Decitabine Induces Antigen-Specific T-lymphocyte Responses in Patients with Myelodysplastic Syndrome.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2018 Mar 01; Vol. 24 (5), pp. 1019-1029. Date of Electronic Publication: 2017 Sep 25. - Publication Year :
- 2018
-
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 + 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 <superscript>+</superscript> and CD8 <superscript>+</superscript> 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 <superscript>Hi</superscript> 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. Clin Cancer Res; 24(5); 1019-29. ©2017 AACR See related commentary by Fuchs, p. 991 .<br /> (©2017 American Association for Cancer Research.)
- Subjects :
- Aged
Antigens, Neoplasm immunology
Antigens, Neoplasm metabolism
Cancer Vaccines immunology
Carboxymethylcellulose Sodium administration & dosage
Carboxymethylcellulose Sodium analogs & derivatives
Combined Modality Therapy methods
Dose-Response Relationship, Drug
Drug Administration Schedule
Feasibility Studies
Humans
Interferon Inducers administration & dosage
Interferon Inducers immunology
Leukemia, Myeloid, Acute immunology
Membrane Proteins antagonists & inhibitors
Membrane Proteins immunology
Membrane Proteins metabolism
Middle Aged
Myelodysplastic Syndromes immunology
Myeloid Cells drug effects
Myeloid Cells immunology
Myeloid Cells metabolism
Poly I-C administration & dosage
Poly I-C immunology
Polylysine administration & dosage
Polylysine analogs & derivatives
Polylysine immunology
T-Lymphocytes, Cytotoxic drug effects
T-Lymphocytes, Cytotoxic immunology
T-Lymphocytes, Cytotoxic metabolism
Treatment Outcome
Antimetabolites, Antineoplastic administration & dosage
Cancer Vaccines administration & dosage
Decitabine administration & dosage
Immunotherapy methods
Leukemia, Myeloid, Acute therapy
Myelodysplastic Syndromes therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3265
- Volume :
- 24
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 28947565
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-17-1792