Epigenetic potentiation of NY-ESO-1 vaccine therapy in human ovarian cancer

Kunle Odunsi, Junko Matsuzaki, Smitha R. James, Paulette Mhawech-Fauceglia, Takemasa Tsuji, Austin Miller, Wa Zhang, Stacey N. Akers, Elizabeth A. Griffiths, Anthony Miliotto, Amy Beck, Carl A. Batt, Gerd Ritter, Shashikant Lele, Sacha Gnjatic, Adam R Karpf

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Abstract

The cancer-testis/cancer-germline antigen NY-ESO-1 is a vaccine target in epithelial ovarian cancer (EOC), but its limited expression is a barrier to vaccine efficacy. As NY-ESO-1 is regulated by DNA methylation, we hypothesized that DNA methyltransferase (DNMT) inhibitors may augment NY-ESO-1 vaccine therapy. In agreement, global DNA hypomethylation in EOC was associated with the presence of circulating antibodies to NY-ESO-1. Pre-clinical studies using EOC cell lines showed that decitabine treatment enhanced both NY-ESO-1 expression and NY-ESO-1-specific CTL-mediated responses. Based on these observations, we performed a phase I dose-escalation trial of decitabine, as an addition to NY-ESO-1 vaccine and doxorubicin liposome (doxorubicin) chemotherapy, in 12 patients with relapsed EOC. The regimen was safe, with limited and clinically manageable toxicities. Both global and promoter-specific DNA hypomethylation occurred in blood and circulating DNAs, the latter of which may reflect tumor cell responses. Increased NY-ESO-1 serum antibodies and T cell responses were observed in the majority of patients, and antibody spreading to additional tumor antigens was also observed. Finally, disease stabilization or partial clinical response occurred in 6/10 evaluable patients. Based on these encouraging results, evaluation of similar combinatorial chemo-immunotherapy regimens in EOC and other tumor types is warranted.

Original languageEnglish (US)
Pages (from-to)37-49
Number of pages13
JournalCancer immunology research
Volume2
Issue number1
DOIs
StatePublished - Jan 1 2014

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Active Immunotherapy
Epigenomics
Ovarian Neoplasms
decitabine
Vaccines
DNA
Testicular Neoplasms
Doxorubicin
Antibodies
Methyltransferases
Neoplasm Antigens
DNA Methylation
Liposomes
Immunotherapy
Neoplasms
Ovarian epithelial cancer
T-Lymphocytes
Antigens
Drug Therapy
Cell Line

ASJC Scopus subject areas

  • Immunology
  • Cancer Research

Cite this

Odunsi, K., Matsuzaki, J., James, S. R., Mhawech-Fauceglia, P., Tsuji, T., Miller, A., ... Karpf, A. R. (2014). Epigenetic potentiation of NY-ESO-1 vaccine therapy in human ovarian cancer. Cancer immunology research, 2(1), 37-49. https://doi.org/10.1158/2326-6066.CIR-13-0126

Epigenetic potentiation of NY-ESO-1 vaccine therapy in human ovarian cancer. / Odunsi, Kunle; Matsuzaki, Junko; James, Smitha R.; Mhawech-Fauceglia, Paulette; Tsuji, Takemasa; Miller, Austin; Zhang, Wa; Akers, Stacey N.; Griffiths, Elizabeth A.; Miliotto, Anthony; Beck, Amy; Batt, Carl A.; Ritter, Gerd; Lele, Shashikant; Gnjatic, Sacha; Karpf, Adam R.

In: Cancer immunology research, Vol. 2, No. 1, 01.01.2014, p. 37-49.

Research output: Contribution to journalArticle

Odunsi, K, Matsuzaki, J, James, SR, Mhawech-Fauceglia, P, Tsuji, T, Miller, A, Zhang, W, Akers, SN, Griffiths, EA, Miliotto, A, Beck, A, Batt, CA, Ritter, G, Lele, S, Gnjatic, S & Karpf, AR 2014, 'Epigenetic potentiation of NY-ESO-1 vaccine therapy in human ovarian cancer', Cancer immunology research, vol. 2, no. 1, pp. 37-49. https://doi.org/10.1158/2326-6066.CIR-13-0126
Odunsi K, Matsuzaki J, James SR, Mhawech-Fauceglia P, Tsuji T, Miller A et al. Epigenetic potentiation of NY-ESO-1 vaccine therapy in human ovarian cancer. Cancer immunology research. 2014 Jan 1;2(1):37-49. https://doi.org/10.1158/2326-6066.CIR-13-0126
Odunsi, Kunle ; Matsuzaki, Junko ; James, Smitha R. ; Mhawech-Fauceglia, Paulette ; Tsuji, Takemasa ; Miller, Austin ; Zhang, Wa ; Akers, Stacey N. ; Griffiths, Elizabeth A. ; Miliotto, Anthony ; Beck, Amy ; Batt, Carl A. ; Ritter, Gerd ; Lele, Shashikant ; Gnjatic, Sacha ; Karpf, Adam R. / Epigenetic potentiation of NY-ESO-1 vaccine therapy in human ovarian cancer. In: Cancer immunology research. 2014 ; Vol. 2, No. 1. pp. 37-49.
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