Title |
Epigenetic Potentiation of NY-ESO-1 Vaccine Therapy in Human Ovarian Cancer
|
---|---|
Published in |
Cancer Immunology Research, January 2014
|
DOI | 10.1158/2326-6066.cir-13-0126 |
Pubmed ID | |
Authors |
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 |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
France | 2 | 25% |
United States | 2 | 25% |
Spain | 1 | 13% |
Belgium | 1 | 13% |
Unknown | 2 | 25% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 6 | 75% |
Practitioners (doctors, other healthcare professionals) | 1 | 13% |
Scientists | 1 | 13% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Netherlands | 1 | <1% |
Unknown | 107 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 19 | 18% |
Researcher | 19 | 18% |
Student > Master | 12 | 11% |
Professor | 9 | 8% |
Student > Bachelor | 6 | 6% |
Other | 18 | 17% |
Unknown | 25 | 23% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 32 | 30% |
Biochemistry, Genetics and Molecular Biology | 18 | 17% |
Immunology and Microbiology | 17 | 16% |
Agricultural and Biological Sciences | 11 | 10% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | <1% |
Other | 3 | 3% |
Unknown | 26 | 24% |