The Immunostimulatory Effect of B16 Freezing/thawing Anti-tumor Vaccine / 체질인류학회지
Korean Journal of Physical Anthropology
; : 115-126, 2007.
Article
Dans Ko
| WPRIM
| ID: wpr-123461
Responsable en Bibliothèque :
WPRO
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.
Texte intégral:
1
Indice:
WPRIM
Sujet Principal:
Cellules dendritiques
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Vaccins
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Cause de décès
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Souris knockout
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Interleukine-12
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Désoxyribonucléases
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Récepteurs de type Toll
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Cellules T tueuses naturelles
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Cardiopathies
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Indicateurs et réactifs
Limites du sujet:
Animals
/
Humans
langue:
Ko
Texte intégral:
Korean Journal of Physical Anthropology
Année:
2007
Type:
Article