A phase II study evaluating the safety and efficacy of an adenovirus-ΔLMP1-LMP2 transduced dendritic cell vaccine in patients with advanced metastatic nasopharyngeal carcinoma
| Autor: | W. K. Chia, W.-W. Wang, W. M. Tai, J. J. Chen, W. T. Lim, L. Sun, Stephen Gottschalk, Han Chong Toh, M. Teo, S. S. Leong, E. H. Tan |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Epstein-Barr Virus Infections Genetic Vectors Nasopharyngeal neoplasm Kaplan-Meier Estimate medicine.disease_cause Cancer Vaccines Disease-Free Survival Adenoviridae Viral Matrix Proteins Immune system Antigen hemic and lymphatic diseases otorhinolaryngologic diseases medicine Humans Epstein–Barr virus infection Cells Cultured Sequence Deletion Nasopharyngeal Carcinoma business.industry Carcinoma Nasopharyngeal Neoplasms Dendritic Cells Original Articles Hematology Dendritic cell Middle Aged medicine.disease Epstein–Barr virus Coculture Techniques stomatognathic diseases Treatment Outcome Oncology Nasopharyngeal carcinoma Delayed hypersensitivity Immunology Female business |
| Zdroj: | Annals of Oncology. 23:997-1005 |
| ISSN: | 0923-7534 |
| DOI: | 10.1093/annonc/mdr341 |
| Popis: | Background: Individuals with metastatic Epstein–Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC) continue to have poor outcomes. To evaluate the ability of a dendritic cell (DC) vaccine to target subdominant EBV antigens LMP1 and LMP2 expressed by NPC cells, we vaccinated patients using autologous DCs transduced with an adenovirus encoding a truncated LMP1 (ΔLMP1) and full-length LMP2 (Ad-ΔLMP1-LMP2). Materials and methods: Sixteen subjects with metastatic NPC received Ad-ΔLMP1-LMP2 DC vaccines i.d. biweekly for up to five doses. Toxicity, immune responses and clinical responses were determined. Results: Most patients had extensive disease, with a median of three visceral sites of involvement (range 1–7). No significant toxicity was observed. Ad-ΔLMP1-LMP2 DCs induced delayed type hypersensitivity responses in 9 out of 12 patients, but although these DCs activated LMP1/2-specific T cells in vitro, no such increase in the frequency of peripheral LMP1/2-specific T cells was detected. Three patients had clinical responses including one with partial response (for 7½ months) and two with stable disease (for 6½ and 7½ months). Conclusions: Ad-ΔLMP1-LMP2 transduced DCs can be successfully generated and safely administered to patients with advanced NPC. Since efficacy was limited, future studies should focus on DC vaccines with greater potency administered to subjects with less tumor burden. |
| Databáze: | OpenAIRE |
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