Adoptive Therapy for EBV-Induced Cancers: Driving Success with Post-Transplant Lymphoproliferative Disorder to Other EBV-Derived Tumors

Smith, Corey; Khanna, Rajiv

doi:10.2217/imt.15.7

Cited by 10 publications

(5 citation statements)

References 68 publications

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“…Previous data demonstrated that primary EBV infection in EBV naive patients is a well‐established risk factor for developing post‐transplant PTLD . Our data support these observations in LTx recipients, with EBV seroconversion in up to 85% prior to PTLD diagnosis.…”

Section: Discussionsupporting

confidence: 88%

Post‐transplant lymphoproliferative disease in lung transplantation: A nested case‐control study

Leyssens

Dierickx

Verbeken

et al. 2017

Clinical Transplantation

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Post-transplant lymphoproliferative disorder (PTLD) may compromise long-term outcome of lung transplant (LTx) recipients. A case-control study was performed, comparing LTx recipients with PTLD (n=31) to matched recipients without PTLD (Controls, n=62). Risk factors for PTLD and post-transplant outcomes were assessed. PTLD prevalence was 3.9%, time to PTLD 323 (166-1132) days; and 54.8% had early-onset PTLD versus 45.2% late-onset PTLD. At LTx, more Epstein-Barr virus (EBV)-seronegative patients were present in PTLD (42%) compared to Controls (5%) (P<.0001); most of whom had undergone EBV seroconversion upon PTLD diagnosis. EBV viral load was higher in PTLD versus Controls (P<.0001). Overall, lower hemoglobin and higher C-reactive protein levels were present in PTLD versus Controls (P<.0001). EBV status at LTx (P=.0073) and EBV viral load at PTLD (P=.0002) were the most important risk determinates for later PTLD. Patients with PTLD demonstrated shorter time to onset of chronic lung allograft dysfunction (CLAD) (P=.0006) and poorer 5-year survival post-LTx (66.6% versus 91.5%), resulting in worse CLAD-free survival (HR 2.127, 95%CI 1.006-4.500; P=.0483) and overall survival (HR 3.297 95%CI 1.473-7.382; P=.0037) compared to Controls. Late-onset PTLD had worse survival compared to early-onset PTLD (P=.021). Primary EBV infection is a risk for PTLD; which is associated with worse long-term outcome post-LTx.

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Section: Discussionsupporting

confidence: 88%

Post‐transplant lymphoproliferative disease in lung transplantation: A nested case‐control study

Leyssens

Dierickx

Verbeken

et al. 2017

Clinical Transplantation

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“…However, the failure to treat locally-aggressive nasopharyngeal carcinoma is not uncommon and distant metastases remains the main cause of death [4]. The strong association of NPC with EBV makes viral antigen-targeted immunotherapy an attractive treatment modality [5]. Adoptive transfer of autologous EBV-specific CTL has proven effective in metastatic or locally recurrent NPC patients [6].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic vaccine targeting Epstein-Barr virus latent protein, LMP1, suppresses LMP1-expressing tumor growth and metastasis in vivo

Lin

Chen

et al. 2017

BMC Cancer

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BackgroundIn endemic area, nasopharyngeal carcinoma (NPC) tumor cells harbor EBV latent infection and expresses viral antigens such as EBNA1, LMP1 and LMP2. In this study, we established a NPC-mimicry animal model and assessed the therapeutic potential of LMP1 vaccine.MethodsAnimal models were established by injection of LMP1-expressing TC-1 cells in C57BL6/J mice subcutaneously or through tail veins. pcDNA3.1 empty vector or LMP1/pcDNA3.1 vaccine was delivered by a helium-driven gene gun. Effectiveness of vaccine was evaluated by measuring the tumor size and numbers of metastatic lung nodules. Circulating cytokines were evaluated by ELISArray. Populations of activated cytotoxic T lymphocytes (CTLs) and LMP1-specific T lymphocytes were evaluated by flow cytometry with CD8/CD107a double staining and interferon-γ ELISPOT assay, respectively.ResultsLMP1 vaccine significantly suppressed tumor growth (n = 3) and metastasis (n = 4) in vivo. When vaccinated before tumor challenge, all mice in vaccine group were tumor-free, whereas all mice in the control group developed tumors within 2 weeks after tumor challenge (n = 10). Cytokine ELISArray revealed elevation of a panel of proinflammatory cytokines in mice receiving LMP1 vaccine. Flow cytometry and interferon-γ ELISPOT assay revealed that LMP1 vaccine induced larger populations of activated CTLs and LMP1-specific T lymphocytes.ConclusionsThis pre-clinical study provides a promising result that LMP1 vaccine suppresses LMP1-expressing tumor growth and metastasis in vivo.

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“…Recently, antitumor immune therapies have shown significant advantages because of their reduced toxicity to mammalian cells . With the increased development of molecular and cellular technologies, new approaches to treat malignancy will be identified.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, antitumor immune therapies have shown significant advantages because of their reduced toxicity to mammalian cells. [48][49][50] With the increased development of molecular and cellular technologies, new approaches to treat malignancy will be identified. FSTL1 can inhibit the migration and proliferation of cancer cells and promote apoptosis, which is beneficial for suppressing carcinoma development.…”

Section: Discussionmentioning

confidence: 99%

Follistatin‐like protein 1 contributes to dendritic cell and T‐lymphocyte activation in nasopharyngeal carcinoma patients by altering nuclear factor κb and Jun N‐terminal kinase expression

Wang

Huang

et al. 2016

Cell Biochemistry & Function

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Follistatin‐like protein 1 (FSTL1) is a newly characterized protein that can regulate the immune response in various ways. Dendritic cells (DCs) are central to immune regulation. In this study, we explored the impact of FSTL1 on DC activity in nasopharyngeal carcinoma (NPC) patients. The surface expression of CD40, CD86, and HLA‐DR on DCs was analyzed and showed significantly elevated expression levels, indicating DC maturity. After FSTL1 was added to DCs collected from NPC patients (n = 50), controls (n = 47), and healthy donors (n = 10), interferon γ secretion and T‐cell receptor expression in cytotoxic T lymphocytes were also investigated. In the experimental groups, the expression of the critical immune protein nuclear factor (NF)‐κb was upregulated, whereas Jun N‐terminal kinase (JNK) was downregulated. Our findings demonstrate that FSTL1 plays a critical role in immune regulation, enhancing the antigen presentation ability of DCs by up‐regulating NF‐κb expression and down‐regulating JNK expression.

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Adoptive Therapy for EBV-Induced Cancers: Driving Success with Post-Transplant Lymphoproliferative Disorder to Other EBV-Derived Tumors

Cited by 10 publications

References 68 publications

Post‐transplant lymphoproliferative disease in lung transplantation: A nested case‐control study

Post‐transplant lymphoproliferative disease in lung transplantation: A nested case‐control study

Therapeutic vaccine targeting Epstein-Barr virus latent protein, LMP1, suppresses LMP1-expressing tumor growth and metastasis in vivo

Follistatin‐like protein 1 contributes to dendritic cell and T‐lymphocyte activation in nasopharyngeal carcinoma patients by altering nuclear factor κb and Jun N‐terminal kinase expression

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