The Immunostimulatory Effect of B16 Freezing/thawing Anti-tumor Vaccine.
10.11637/kjpa.2007.20.2.115
- Author:
Daesun YUN
1
;
Jeehee YOUN
;
Seokmann HONG
Author Information
1. Department of Bioscience and Biotechnology, Sejong University, Korea. shong@sejong.ac.kr
- Publication Type:Original Article
- Keywords:
B16 F/T anti-tumor vaccine;
Fluorescent reporter mouse system;
Interleukin 12;
Toll-like receptor
- MeSH:
Animals;
Cause of Death;
Dendritic Cells;
Deoxyribonucleases;
Heart Diseases;
Humans;
Indicators and Reagents;
Interleukin-12;
Mice;
Mice, Knockout;
Natural Killer T-Cells;
Toll-Like Receptors;
Vaccines
- From:Korean Journal of Physical Anthropology
2007;20(2):115-126
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
Since cancer has become the second most common cause of death, next to heart disease and approximately 20% of human population dies from cancer, it is much desired to develop therapeutic anti-tumor vaccine with safety and efficacy. Here we investigated the immunostimulatory effects of B16 freezing/thawing (F/T) anti-tumor vaccine (hereafter F/T vaccine), one of whole cell anti-tumor vaccines. To this end, we took advantage of the IL12 p40 reporter system which is designed for monitoring the induction of IL12 expression via the detection of co-expressed yellow fluorescent protein. First, we examined whether F/T vaccine can induce IL12 expression using bone marrow-derived dendritic cells (BMDCs) from IL12 p40 reporter mice. Second, we examined whether F/T vaccine can change the expression level of MHC molecules and co-stimulatory molecules during the activation of dendritic cells. Third, to dissect what component of F/T vaccines accounts for the immunostimulatory activities, we examined the effect of F/T vaccine on BMDC activation after treating it with DNase or proteinase. Lastly, we used MyD88 knockout mice to investigate whether F/T vaccine activates BMDCs in a TLRdependent manner. We found that treatment of BMDCs with F/T vaccine induced IL12 expression as well as the increase of MHC II expression and co-stimulatory molecules such as CD86. Interestingly, we also found that F/T vaccine increased CD1d expression on BMDCs, which may influence the activation of natural killer T cells known to be involved in anti-tumor immune responses. In addition, we found that treatment of F/T vaccine with proteinase but not DNase abolished its immunostimulatory effect, indicating that proteins in F/T vaccine mainly have its adjuvant activity. Furthermore, the activation of BMDCs with F/T vaccine was dependent on MyD88 adaptor molecule. Taken together, our findings in this study demonstrated that the F/T vaccine might be one of the valuable reagents to provide a new insight for underlying mechanism of whole-cell anti-tumor vaccines and an important clue for the development of better therapeutic anti-cancer vaccines.
