2011
DOI: 10.1158/1078-0432.ccr-11-1873
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Improving T-cell Therapy for Relapsed EBV-Negative Hodgkin Lymphoma by Targeting Upregulated MAGE-A4

Abstract: Rationale Patients with Hodgkin’s Lymphoma (HL) relapsing after hematopoietic stem cell transplant (HSCT) 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. Furt… Show more

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Cited by 71 publications
(54 citation statements)
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“…Of note, its ability to induce expression of cancer-testis antigens (19,27), most notably NY-ESO-1, for improved vaccination of ovarian cancer patients (28), is well established. Microarray analysis DMSO + α-CTLA-4 **** ** Figure 5.…”
Section: Discussionmentioning
confidence: 99%
“…Of note, its ability to induce expression of cancer-testis antigens (19,27), most notably NY-ESO-1, for improved vaccination of ovarian cancer patients (28), is well established. Microarray analysis DMSO + α-CTLA-4 **** ** Figure 5.…”
Section: Discussionmentioning
confidence: 99%
“…Hypomethylating agents may increase tumor antigen expression, leading to more diverse antigen-specific responses that can prevent immune escape. 120 HDAC inhibition also suppresses RS production of multiple cytokines and chemokines favoring Th2 cell recruitment and differentiation. For example, the treatment of CHL cell lines with vorinostat was shown to reduce STAT-mediated production of Th2 polarizing cytokines IL-5, IL-10 and IL-13 as well as the Th2 recruiting chemokine TARC.…”
Section: Towards Rational Combination Strategies In Hodgkin Lymphomamentioning
confidence: 99%
“…T cells targeting multiple proteins have been generated using this method, 20 and further increases in antigen can be accomplished in vivo using epigenetic modifying drugs. 76,77 (v) Engineering resistance to immune suppression. Finally, efforts are also underway to confer greater resistance to cells against the immunosuppressive microenvironment mediated by tumors.…”
Section: Future Directionsmentioning
confidence: 99%