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


Personal Author(s) : Chung, David J


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a581991.pdf


Report Date : Jul 2013


Pagination or Media Count : 15


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 CD4+/CD8+ 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.


Descriptors :   *CANCER , *CELLS(BIOLOGY) , *INFECTIOUS DISEASES , *LISTERIA , *VACCINES , ANTIGENS , BASE LINES , CYTOKINES , ENZYMES , IMMUNITY , IMMUNOGENS , IMMUNOSUPPRESSION , POTENCY , RESPONSE(BIOLOGY) , STIMULATION(PHYSIOLOGY) , THERAPY


Subject Categories : Medicine and Medical Research
      Microbiology


Distribution Statement : APPROVED FOR PUBLIC RELEASE