Improving T-cell Therapy for Relapsed EBV-Negative Hodgkin Lymphoma by Targeting Upregulated MAGE-A4

摘要: Purpose: Patients with Hodgkin lymphoma (HL) relapsing after hematopoietic stem cell transplant have limited options for long-term cure. We 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 up to 70% relapsed tumors are EBV-negative. For these patients, an alternative target the cancer/testis antigen MAGE-A4 present antigen-negative tumors. Furthermore, epigenetic modification by clinically available demethylating agents can enhance expression previously MAGE-negative Experimental Design: explored feasibility combining adoptive therapy tumor expression. further characterized MAGE-A4–specific T-cell phenotype and function, examined effects modifying drug decitabine on cells. Results: Cytotoxic were generated specifically recognizing expressed autologous targets lines. Decitabine—previously increase HL—did not compromise function. In patients treated decitabine, expanded had a broader antitumor repertoire, consistent increased stimulation vivo . Conclusions: Adoptive transfer cells, combined drugs protein, may improve treatment HL. Clin Cancer Res; 17(22); 7058–66. ©2011 AACR