Evaluation of Immune Responses Mediated by Listeria-Stimulated Human Dendritic Cells: Implications for Cancer Vaccine Therapy
Annual rept. 15 Jun 2012-14 Jun 2013
SLOAN-KETTERING INST FOR CANCER RESEARCH NEW YORK
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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.
- Medicine and Medical Research