FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2557805959> ?p ?o ?g. }

• W2557805959 abstract "Abstract Abstract 1658 Patients with Hodgkin's Lymphoma (HL) who relapse after hematopoietic stem cell transplant (HSCT) have limited options for long-term cure. We have shown that infusion of 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 strategy is to target the cancer/testis antigen MAGE-A4 which is present in EBV antigen-negative Hodgkin's lymphoma tumors. Furthermore, epigenetic modification by clinically available demethylating agents can enhance MAGE-A4 expression in previously MAGE-negative tumors. We explored the feasibility of combining adoptive T-cell therapy with epigenetic modification of tumor antigen expression. We first verified whether MAGE-A4-specific CTL could be expanded from autologous and allogeneic donors. Dendritic cells from healthy donors (n=15) or HL patients (n=9) were pulsed with overlapping peptides spanning the MAGE-A4 protein. Healthy donor T-cell lines expanded to sufficient numbers for clinical use and predominantly comprised CD8+ cytotoxic T cells (mean 60%; range 42–81%) and CD4+ T helper cells (mean 20%; range 8–45%). A mean response of 152 interferon gamma (IFNγ) spot forming cells (SFC)/1 × 105 cells (median 78; range 12–635) was observed against MAGE-A4 peptides compared to a mean of 6 IFNγ SFC/1×105 cells (median 4; range 0–30) to irrelevant peptides. Both CD4+ and CD8+ T cell subsets contributed to the interferon response. In T cells expanded from the peripheral blood of patients with HL, a mean of 296 SFC/1×105 cells (range 32–1031) responded to MAGE-A4 peptides compared to a mean of 5 SFC/1×105 cells (range 1–11) responding to irrelevant targets. Five of fifteen CTL lines generated from healthy donors showed specificity for a particular peptide (aa266-285, NPARYEFLWGPRALAETSYV). In contrast, T-cell lines derived from HL patients showed a range of MAGE-A4 epitope specificities. Peripheral blood mononuclear cell and dendritic cell numbers were reduced, and T cells from these patients failed to expand after several stimulations consistent with the profound immune deficiency frequently seen in HL patients. We next evaluated the effect of combining MAGE-CTL with the epigenetic-modifying demethylating agent 2'-deoxy-5'azacytidine. To determine if decitabine would negatively affect the function of the TAA-specific T cells, we examined the effects of the drug on the function of MAGEA4-specific T cells in vitro. Our results showed that treatment of T cells with decitabine – in concentrations that exceed expected levels following drug treatment (1 μM) - did not adversely affect the phenotype and function of MAGE-A4 specific T cells in vitro. To evaluate the in vivo effects of decitabine on tumor antigen specific T cells, patient samples were obtained before and after treatment. In patients who received a decitabine containing regimen (75 mg/m2 daily × 5 days) (n=2), one of whom had clinical responses on PET scan, we observed that MAGE-specific T cells were of greater magnitude and recognized a broader number of MAGE-A4 epitopes after decitabine treatment (see Figure below – a and b are patients with a decitabine containing regimen; c and d are patients receiving no decitabine). In patients (n= 2) who did not receive a decitabine containing regimen, the magnitude of MAGE-specific reactivity was reduced, as measured by IFNγ Elispot. These results suggest that although decitabine may modulate immune function, the effect of other chemotherapies may result in the lack of appreciable endogenous T-cell responses to tumor antigens in these patients. Hence, adoptive transfer of MAGE-A4 specific T cells combined with the administration of epigenetic-modifying drugs to increase expression of the target antigens may improve the efficacy of treatment of relapsed Hodgkin's Lymphoma. Disclosures: Younes: Celgene: Speakers Bureau; Syndax: Research Funding; SBIO: Research Funding; Genentech: Research Funding; Sanofi-Aventis: Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; Seattle Genetics, Inc.: Consultancy, Honoraria, Research Funding, Speakers Bureau, Travel Expenses; Gilead: Honoraria; Pharmacyclic: Honoraria." @default.
• W2557805959 created "2016-12-08" @default.
• W2557805959 creator A5006134549 @default.
• W2557805959 creator A5020956671 @default.
• W2557805959 creator A5021029688 @default.
• W2557805959 creator A5026118697 @default.
• W2557805959 creator A5033997937 @default.
• W2557805959 creator A5043489790 @default.
• W2557805959 creator A5057196933 @default.
• W2557805959 creator A5065054247 @default.
• W2557805959 creator A5067486820 @default.
• W2557805959 creator A5068152076 @default.
• W2557805959 creator A5073212086 @default.
• W2557805959 creator A5087013892 @default.
• W2557805959 date "2011-11-18" @default.
• W2557805959 modified "2023-09-26" @default.
• W2557805959 title "Improving T Cell Therapy for Relapsed EBV-Negative Hodgkin's Lymphoma by Targeting Upregulated MAGE-A4" @default.
• W2557805959 doi "https://doi.org/10.1182/blood.v118.21.1658.1658" @default.
• W2557805959 hasPublicationYear "2011" @default.
• W2557805959 type Work @default.
• W2557805959 sameAs 2557805959 @default.
• W2557805959 citedByCount "0" @default.
• W2557805959 crossrefType "journal-article" @default.
• W2557805959 hasAuthorship W2557805959A5006134549 @default.
• W2557805959 hasAuthorship W2557805959A5020956671 @default.
• W2557805959 hasAuthorship W2557805959A5021029688 @default.
• W2557805959 hasAuthorship W2557805959A5026118697 @default.
• W2557805959 hasAuthorship W2557805959A5033997937 @default.
• W2557805959 hasAuthorship W2557805959A5043489790 @default.
• W2557805959 hasAuthorship W2557805959A5057196933 @default.
• W2557805959 hasAuthorship W2557805959A5065054247 @default.
• W2557805959 hasAuthorship W2557805959A5067486820 @default.
• W2557805959 hasAuthorship W2557805959A5068152076 @default.
• W2557805959 hasAuthorship W2557805959A5073212086 @default.
• W2557805959 hasAuthorship W2557805959A5087013892 @default.
• W2557805959 hasConcept C104317684 @default.
• W2557805959 hasConcept C147483822 @default.
• W2557805959 hasConcept C147969180 @default.
• W2557805959 hasConcept C150194340 @default.
• W2557805959 hasConcept C154317977 @default.
• W2557805959 hasConcept C167672396 @default.
• W2557805959 hasConcept C190727270 @default.
• W2557805959 hasConcept C202751555 @default.
• W2557805959 hasConcept C203014093 @default.
• W2557805959 hasConcept C2776090121 @default.
• W2557805959 hasConcept C2779277951 @default.
• W2557805959 hasConcept C2779338263 @default.
• W2557805959 hasConcept C502942594 @default.
• W2557805959 hasConcept C55493867 @default.
• W2557805959 hasConcept C71924100 @default.
• W2557805959 hasConcept C86803240 @default.
• W2557805959 hasConcept C8891405 @default.
• W2557805959 hasConceptScore W2557805959C104317684 @default.
• W2557805959 hasConceptScore W2557805959C147483822 @default.
• W2557805959 hasConceptScore W2557805959C147969180 @default.
• W2557805959 hasConceptScore W2557805959C150194340 @default.
• W2557805959 hasConceptScore W2557805959C154317977 @default.
• W2557805959 hasConceptScore W2557805959C167672396 @default.
• W2557805959 hasConceptScore W2557805959C190727270 @default.
• W2557805959 hasConceptScore W2557805959C202751555 @default.
• W2557805959 hasConceptScore W2557805959C203014093 @default.
• W2557805959 hasConceptScore W2557805959C2776090121 @default.
• W2557805959 hasConceptScore W2557805959C2779277951 @default.
• W2557805959 hasConceptScore W2557805959C2779338263 @default.
• W2557805959 hasConceptScore W2557805959C502942594 @default.
• W2557805959 hasConceptScore W2557805959C55493867 @default.
• W2557805959 hasConceptScore W2557805959C71924100 @default.
• W2557805959 hasConceptScore W2557805959C86803240 @default.
• W2557805959 hasConceptScore W2557805959C8891405 @default.
• W2557805959 hasLocation W25578059591 @default.
• W2557805959 hasOpenAccess W2557805959 @default.
• W2557805959 hasPrimaryLocation W25578059591 @default.
• W2557805959 hasRelatedWork W180849893 @default.
• W2557805959 hasRelatedWork W2030174805 @default.
• W2557805959 hasRelatedWork W2036834310 @default.
• W2557805959 hasRelatedWork W2130309988 @default.
• W2557805959 hasRelatedWork W2312168204 @default.
• W2557805959 hasRelatedWork W2398980363 @default.
• W2557805959 hasRelatedWork W2490293660 @default.
• W2557805959 hasRelatedWork W2550354355 @default.
• W2557805959 hasRelatedWork W2560452776 @default.
• W2557805959 hasRelatedWork W2567914701 @default.
• W2557805959 hasRelatedWork W2580732433 @default.
• W2557805959 hasRelatedWork W2904224777 @default.
• W2557805959 hasRelatedWork W2905913126 @default.
• W2557805959 hasRelatedWork W2914219564 @default.
• W2557805959 hasRelatedWork W2943343016 @default.
• W2557805959 hasRelatedWork W2979691690 @default.
• W2557805959 hasRelatedWork W2979728626 @default.
• W2557805959 hasRelatedWork W2990521001 @default.
• W2557805959 hasRelatedWork W3007938849 @default.
• W2557805959 hasRelatedWork W3096647038 @default.
• W2557805959 isParatext "false" @default.
• W2557805959 isRetracted "false" @default.
• W2557805959 magId "2557805959" @default.
• W2557805959 workType "article" @default.