DID YOU KNOW? DTIC has over 3.5 million final reports on DoD funded research, development, test, and evaluation activities available to our registered users. Click
HERE to register or log in.
Accession Number:
ADA581991
Title:
Evaluation of Immune Responses Mediated by Listeria-Stimulated Human Dendritic Cells: Implications for Cancer Vaccine Therapy
Descriptive Note:
Annual rept. 15 Jun 2012-14 Jun 2013
Corporate Author:
SLOAN-KETTERING INST FOR CANCER RESEARCH NEW YORK
Report Date:
2013-07-01
Pagination or Media Count:
15.0
Abstract:
The purpose of this project is to study the immunomodulatory effect of Listeria on human dendritic cells DCs to optimize Listeria-based DC cancer vaccines. The project aims are 1 Compare the activation and maturation of different human DC subsets in response to Listeria infection. 2 Define the induction of CD4CD8 T-cell and NK cell responses to Listeriaactivated DCs presenting a melanoma tumor-associated antigen. 3 Augment the immunogenicity of Listeria-activated DCs by inhibiting the immunosuppressive enzyme, indoleamine 2,3-dioxygenase. During the initial period of funding, critical parameters and baseline readouts of Listeria infection of monocyte-derived DCs moDCs were identified and validated. Key findings include 1 Listeria treatment induces DC maturation and activation. 2 Listeria-treated DCs are functionally active, potent stimulators of T-cell proliferation. 3 Listeria treatment does not promote the over-expression of inhibitory markers on DCs. 4 Listeria treatment does not potentiate the expansion of immune-dampening regulatory T-cells by DCs. 5 Listeriatreated moDCs, without exogenous cytokine supplementation, are potent stimulators of antigen-specific CTLs. These findings confirm the immune-stimulatory properties of Listeria as a vaccine adjuvant. Studies of the mechanisms of Listeriainduced immunity and optimization of Listeria-based DC vaccines are ongoing.
Distribution Statement:
APPROVED FOR PUBLIC RELEASE