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

Lin, Mei-Chun; Lin, Yong-Chong; Chen, Syue-Ting; Young, Tai‐Horng; Lou, Pei‐Jen

doi:10.1186/s12885-016-3027-1

Cited by 23 publications

(18 citation statements)

References 31 publications

(39 reference statements)

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“…287 The construction of in vivo models could be divided into spontaneous models, induced models, transplantation models, and transgenic models. [288][289][290][291][292] Spontaneous models are rarely obtained and utilized. 288 Induction conforms to the characteristics of tumor dynamics and is often used to screen carcinogens but seldom used in targeted therapy for NPC.…”

Section: Discussionmentioning

confidence: 99%

Advances in targeted therapy mainly based on signal pathways for nasopharyngeal carcinoma

Kang

Ren

et al. 2020

Sig Transduct Target Ther

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Nasopharyngeal carcinoma (NPC) is a malignant epithelial carcinoma of the head and neck region which mainly distributes in southern China and Southeast Asia and has a crucial association with the Epstein–Barr virus. Based on epidemiological data, both incidence and mortality of NPC have significantly declined in recent decades grounded on the improvement of living standard and medical level in an endemic region, in particular, with the clinical use of individualized chemotherapy and intensity-modulated radiotherapy (IMRT) which profoundly contributes to the cure rate of NPC patients. To tackle the challenges including local recurrence and distant metastasis in the current NPC treatment, we discussed the implication of using targeted therapy against critical molecules in various signal pathways, and how they synergize with chemoradiotherapy in the NPC treatment. Combination treatment including targeted therapy and IMRT or concurrent chemoradiotherapy is presumably to be future options, which may reduce radiation or chemotherapy toxicities and open new avenues for the improvement of the expected functional outcome for patients with advanced NPC.

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Section: Discussionmentioning

confidence: 99%

Advances in targeted therapy mainly based on signal pathways for nasopharyngeal carcinoma

Kang

Ren

et al. 2020

Sig Transduct Target Ther

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“…For examples, Fu and colleagues demonstrated that EBNA1 peptide-loaded DCs vaccine elicited CD4+ T-cells responses and tumour growth inhibition using several EBNA1-expressing BL mouse models including wild-type B6, CD8-deficient, and MHC class I-deficient mice [ 66 ]. Recently, Lin and coworkers successfully suppressed LMP1-enhanced NPC tumour growth and metastasis by injecting LMP1 vaccine into C57BL6/J mice [ 16 ]. Furthermore, the LMP1 vaccine was able to prevent LMP1-expressing tumour development when it was given before tumour challenge [ 16 ].…”

Section: Challenges and Future Perspectivesmentioning

confidence: 99%

“…Recently, Lin and coworkers successfully suppressed LMP1-enhanced NPC tumour growth and metastasis by injecting LMP1 vaccine into C57BL6/J mice [ 16 ]. Furthermore, the LMP1 vaccine was able to prevent LMP1-expressing tumour development when it was given before tumour challenge [ 16 ]. Notably, the outcome of animal model is important to test out the feasibility of new immunotherapy or vaccine, but it must not be related to any of clinical trial outcomes due to the biological variations across different models.…”

Section: Challenges and Future Perspectivesmentioning

confidence: 99%

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Epstein-Barr Virus as a Promising Immunotherapeutic Target for Nasopharyngeal Carcinoma Treatment

Teow

Yap

Peh

2017

Journal of Pathogens

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Epstein-Barr virus (EBV) is a pathogen that infects more than 90% of global human population. EBV primarily targets B-lymphocytes and epithelial cells while some of them infect monocyte/macrophage, T-lymphocytes, and dendritic cells (DCs). EBV infection does not cause death by itself but the infection has been persistently associated with certain type of cancers such as nasopharyngeal carcinoma (NPC), Burkitt's lymphoma (BL), and Hodgkin's lymphoma (HL). Recent findings have shown promise on targeting EBV proteins for cancer therapy by immunotherapeutic approach. Some studies have also shown the success of adopting EBV-based therapeutic vaccines for the prevention of EBV-associated cancer particularly on NPC. In-depth investigations are in progress to refine the current therapeutic and vaccination strategies. In present review, we discuss the highly potential EBV targets for NPC immunotherapy and therapeutic vaccine development as well as addressing the underlying challenges in the process of bringing the therapy and vaccination from the bench to bedside.

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“…DNA vaccines have previously reported interesting responses against LMP1 [28] and LMP2 [29] in mouse models. This study furthers this research by exploring the immune responses to a combination of EBV latent proteins using newly designed synthetic DNA-encoded antigens studied in the context of facilitated in vivo local delivery.…”

Section: Introductionmentioning

confidence: 99%

Novel Synthetic DNA Immunogens Targeting Latent Expressed Antigens of Epstein–Barr Virus Elicit Potent Cellular Responses and Inhibit Tumor Growth

2019

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Infectious diseases are linked to 15%–20% of cancers worldwide. Among them, Epstein–Barr virus (EBV) is an oncogenic herpesvirus that chronically infects over 90% of the adult population, with over 200,000 cases of cancer and 150,000 cancer-related deaths attributed to it yearly. Acute EBV infection can present as infectious mononucleosis, and lead to the future onset of multiple cancers, including Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, and gastric carcinoma. Many of these cancers express latent viral genes, including Epstein–Barr virus nuclear antigen 1 (EBNA1) and latent membrane proteins 1 and 2 (LMP1 and LMP2). Previous attempts to create potent immunogens against EBV have been reported but generated mixed success. We designed novel Synthetic Consensus (SynCon) DNA vaccines against EBNA1, LMP1 and LMP2 to improve on the immune potency targeting important antigens expressed in latently infected cells. These EBV tumor antigens are hypothesized to be useful targets for potential immunotherapy of EBV-driven cancers. We optimized the genetic sequences for these three antigens, studied them for expression, and examined their immune profiles in vivo. We observed that these immunogens generated unique profiles based on which antigen was delivered as the vaccine target. EBNA1vax and LMP2Avax generated the most robust T cell immunity. Interestingly, LMP1vax was a very weak immunogen, generating very low levels of CD8 T cell immunity both as a standalone vaccine and as part of a trivalent vaccine cocktail. LMP2Avax was able to drive immunity that impacted EBV-antigen-positive tumor growth. These studies suggest that engineered EBV latent protein vaccines deserve additional study as potential agents for immunotherapy of EBV-driven cancers.

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

Cited by 23 publications

References 31 publications

Advances in targeted therapy mainly based on signal pathways for nasopharyngeal carcinoma

Advances in targeted therapy mainly based on signal pathways for nasopharyngeal carcinoma

Epstein-Barr Virus as a Promising Immunotherapeutic Target for Nasopharyngeal Carcinoma Treatment

Novel Synthetic DNA Immunogens Targeting Latent Expressed Antigens of Epstein–Barr Virus Elicit Potent Cellular Responses and Inhibit Tumor Growth

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