CD40L-adjuvanted DNA vaccine carrying EBV-LMP2 antigen enhances anti-tumor effect in NPC transplantation tumor animal

Lei, Lei; Liu, Meiqing; Hu, Xiaoming; Zhou, Yue; Yang, Shiming

doi:10.5114/ceji.2018.77379

Cited by 6 publications

(1 citation statement)

References 23 publications

(22 reference statements)

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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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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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Dendritic Cell Vaccines

Schachter

2021

Blood and Marrow Transplant Handbook

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A lipid-based LMP2-mRNA vaccine to treat nasopharyngeal carcinoma

et al. 2023

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Nasopharyngeal carcinoma (NPC) is a serious and highly invasive epithelial malignancy that is closely associated with Epstein—Barr virus (EBV). Due to the lack of therapeutic vaccines for NPC, we selected EBV latent membrane protein 2 (LMP2) as a preferable targeting antigen to develop a lipid-based LMP2-mRNA (mLMP2) vaccine. Full-length mLMP2 expressing LMP2 was first synthesized using an in vitro transcription method and then encapsulated into (2,3-dioleacyl propyl) trimethylammonium chloride (DOTAP)-based cationic liposomes to obtain the mRNA vaccine (LPX-mLMP2). The cell assays showed that the antigen-presenting cells were capable of highly efficient uptake of LPX-mLMP2 and expression of LMP2. LMP2 could subsequently be presented to form the peptide-major histocompatibility complex (pMHC). Furthermore, LPX-mLMP2 could accumulate in the spleen, express antigens, promote the maturation of dendritic cells and stimulate antigen-specific T-cell responses in vivo. It dramatically inhibited the tumor growth of the LMP2-expressing tumor model after three doses of vaccination. Additionally, the proliferation of antigen-specific T cells in the tumor site made a good sign for the promise of mRNA vaccines in virus-induced cancer. Overall, we provided a newly developed antigen-encoding mRNA vaccine with advantages against NPC. We also demonstrated that mRNA vaccines are attractive candidates for cancer immunotherapy. Electronic Supplementary Material Supplementary material (methods of cytotoxicity assay, LMP2 expression, hemolysis test, the results of purity and maturity of BMDCs, LMP2 expression, and evaluation of T cells in lymph nodes and gating strategy for CTLs) is available in the online version of this article at 10.1007/s12274-022-5254-x.

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CD40L-adjuvanted DNA vaccine carrying EBV-LMP2 antigen enhances anti-tumor effect in NPC transplantation tumor animal

Cited by 6 publications

References 23 publications

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

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

Dendritic Cell Vaccines

A lipid-based LMP2-mRNA vaccine to treat nasopharyngeal carcinoma

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