| Improving T-cell therapy for relapsed EBV-negative Hodgkin lymphoma by targeting upregulated MAGE-A4. | |
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MedLine Citation:
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PMID: 21908573 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: Patients with Hodgkin lymphoma (HL) relapsing after hematopoietic stem cell transplant have limited options for long-term cure. We have shown that infused cytotoxic T cells (CTL) targeting Epstein Barr virus (EBV)-derived proteins induced complete remissions in EBV(+) HL patients. A limitation of this approach is that up to 70% of relapsed HL tumors are EBV-negative. For these patients, an alternative is to target the cancer/testis antigen MAGE-A4 present in EBV antigen-negative HL tumors. Furthermore, epigenetic modification by clinically available demethylating agents can enhance MAGE-A4 expression in previously MAGE-negative tumors. EXPERIMENTAL DESIGN: We explored the feasibility of combining adoptive T cell therapy with epigenetic modification of tumor antigen expression. We further characterized MAGE-A4-specific T-cell phenotype and function, and examined the effects of the epigenetic modifying drug decitabine on these T cells. RESULTS: Cytotoxic T cells were generated specifically recognizing MAGE-A4 expressed by autologous HL targets and tumor cell lines. Decitabine-previously shown to increase tumor antigen expression in HL-did not compromise MAGE-A4-specific T-cell phenotype and function. In patients treated with decitabine, expanded MAGE-A4-specific T cells had a broader antitumor T cell repertoire, consistent with increased antigen stimulation in vivo. CONCLUSIONS: Adoptive transfer of MAGE-A4-specific T cells, combined with epigenetic modifying drugs to increase expression of the protein, may improve treatment of relapsed HL. |
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Authors:
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Conrad R Cruz; Ulrike Gerdemann; Ann M Leen; Jessica A Shafer; Stephanie Ku; Benjamin Tzou; Terzah M Horton; Andrea Sheehan; Amanda Copeland; Anas Younes; Cliona M Rooney; Helen E Heslop; Catherine M Bollard |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-09-09 |
Journal Detail:
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Title: Clinical cancer research : an official journal of the American Association for Cancer Research Volume: 17 ISSN: 1078-0432 ISO Abbreviation: Clin. Cancer Res. Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-17 Completed Date: 2012-03-25 Revised Date: 2013-05-15 |
Medline Journal Info:
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Nlm Unique ID: 9502500 Medline TA: Clin Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 7058-66 Citation Subset: IM |
Affiliation:
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Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antigens, Neoplasm
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metabolism* Antimetabolites, Antineoplastic / therapeutic use* Azacitidine / analogs & derivatives*, pharmacology, therapeutic use Cell Line, Tumor Epigenesis, Genetic Epitopes Feasibility Studies Herpesvirus 4, Human / isolation & purification Hodgkin Disease / immunology, therapy*, virology Humans Immunotherapy, Adoptive / methods* Molecular Targeted Therapy Neoplasm Proteins / metabolism* Recurrence T-Lymphocytes / drug effects, immunology, transplantation* Up-Regulation |
| Grant Support | |
ID/Acronym/Agency:
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P50 CA126752/CA/NCI NIH HHS; P50 CA126752-01/CA/NCI NIH HHS; P50CA126752/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, Neoplasm; 0/Antimetabolites, Antineoplastic; 0/Epitopes; 0/MAGEA4 protein, human; 0/Neoplasm Proteins; 2353-33-5/decitabine; 320-67-2/Azacitidine |
| Comments/Corrections | |
Comment In:
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Clin Cancer Res. 2011 Nov 15;17(22):6955-7
[PMID:
22068655
]
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Erratum In:
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Clin Cancer Res. 2012 Feb 1;18(3):913 Note: Dosage error in article text |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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