DNA vaccine with α-galactosylceramide at prime phase enhances anti-tumor immunity after boosting with antigen-expressing dendritic cells.

Abstract

DNA vaccines contribute to a promising new approach for the generation of cytotoxic T lymphocytes (CTL). DNA vaccines do have several disadvantages, including poor immunogenicity and oncogene expression. We used the natural killer T-cell (NKT) ligand α-galactosylceramide (α-GalCer) as an adjuvant to prime initial DNA vaccination; and used the potent immune-stimulatory tumor antigen-expressing dendritic cells (DCs) as a booster vaccination. A DNA vaccine expressing human papillomavirus (HPV) type 16 E7 (pcDNA3-CRT/E7) was combined with α-GalCer at the prime phase, and generated a higher number of E7-specific CD8(+) T-cells in vaccinated mice than vaccine used at boost phase. Therefore, priming with a DNA vaccine in the presence of α-GalCer and boosting with E7-pulsed DC-1 led to a significant enhancement of E7-specific CD8(+) effector and memory T-cells as well as significantly improved therapeutic and preventive effects against an E7-expressing tumor model (TC-1) in vaccinated mice. Our findings suggested that the potency of a DNA vaccine combined with α-GalCer could be further enhanced by boosting with an antigen-expressing DC-based vaccine to generate anti-tumor immunity.

• Authors: Daejin Kim, Chien-Fu Hung, T-C Wu, Yeong-Min Park
• Journal: Vaccine (Vaccine) Vol. 28 Issue 45 Pg. 7297-305 (Oct 21 2010) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 20817010 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Adjuvants, Immunologic
• Cancer Vaccines
• Cytokines
• Galactosylceramides
• Papillomavirus E7 Proteins
• Vaccines, DNA
• alpha-galactosylceramide
• oncogene protein E7, Human papillomavirus type 16

Topics

• Adjuvants, Immunologic (administration & dosage)
• Animals
• CD8-Positive T-Lymphocytes (immunology)
• Cancer Vaccines (immunology)
• Cell Line, Tumor
• Cytokines (immunology)
• Dendritic Cells (immunology)
• Female
• Galactosylceramides (administration & dosage, immunology)
• Immunization, Secondary
• Mice
• Mice, Inbred C57BL
• Neoplasms, Experimental (immunology, prevention & control)
• Papillomavirus E7 Proteins (immunology)
• Spleen (cytology)
• Vaccines, DNA (immunology)