Novel Approach to the Formulation of an Epstein-Barr Virus Antigen-Based Nasopharyngeal Carcinoma Vaccine
| Autor: | Leanne E. Morrison, Scott Thomson, Lea Heslop, David F. Hall, William B. Coman, Pauline Crooks, Viviana P. Lutzky, Denis J. Moss, Monika Corban |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
CD4-Positive T-Lymphocytes
Herpesvirus 4 Human medicine.medical_treatment Immunology Nasopharyngeal neoplasm CD8-Positive T-Lymphocytes Biology medicine.disease_cause Cancer Vaccines Microbiology Epitope Herpesviridae Viral Matrix Proteins Epitopes Antigen Cancer immunotherapy Virology Vaccines and Antiviral Agents otorhinolaryngologic diseases medicine Humans Antigens Viral Cells Cultured Nasopharyngeal Neoplasms medicine.disease Epstein–Barr virus stomatognathic diseases Epstein-Barr Virus Nuclear Antigens Nasopharyngeal carcinoma Insect Science Leukocytes Mononuclear Cancer vaccine T-Lymphocytes Cytotoxic |
| Zdroj: | Journal of Virology. 84:407-417 |
| ISSN: | 1098-5514 0022-538X |
| Popis: | Epstein-Barr virus (EBV) is associated with several malignant diseases including nasopharyngeal carcinoma (NPC), a common neoplasm throughout southeast Asia. Radiotherapy and chemotherapy can achieve remission, but a reemergence of disease is not uncommon. Therefore, there is a need for specific therapies that target the tumor through the recognition of EBV antigens. In NPC, latent membrane protein 1 (LMP1) and LMP2 offer the best opportunity for specific targeting since they are typically expressed and T-cell determinants in each of these proteins have been defined. We have attempted to maximize the opportunity of incorporating every possible CD4 and CD8 determinant in a single formulation. We have achieved this by generating a scrambled protein incorporating random overlapping peptide sets from EBNA1, LMP1, and LMP2, which was then inserted into a replication-deficient strain of adenovirus (adenovirus scrambled antigen vaccine [Ad-SAVINE]). This report describes the construction of this Ad-SAVINE construct, its utility in generating LMP1 and LMP2 responses in healthy individuals as well as NPC patients, and its capacity to define new epitopes. This formulation could have a role in NPC immunotherapy for all ethnic groups since it has the potential to activate all possible CD4 and CD8 responses within EBNA1 and LMPs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|