Journal
CLINICAL CANCER RESEARCH
Volume 17, Issue 22, Pages 7058-7066Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-11-1873
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Funding
- NIH SPORE [P50CA126752]
- Leukemia Lymphoma Society
- Bear Necessities Pediatric Cancer Foundation
- Cancer Prevention Research Institute of Texas
- Leukemia and Lymphoma Society
- Gillson Longenbaugh Foundation
- Carl C. Anderson, Sr. and Marie Jo Anderson Charitable Foundation
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Purpose: Patients with Hodgkin lymphoma (HL) relapsing after hematopoietic stem cell transplant have limited options for long-term cure. Wehave 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 inHL-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. Clin Cancer Res; 17(22); 7058-66. (C) 2011 AACR.
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