Evaluation of Immune Responses Mediated by Listeria-Stimulated Human Dendritic Cells: Implications for Cancer Vaccine Therapy
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 infection, including that mediated by attenuated strains, induces moDC maturation and activation. 2) Listeria-treated moDCs are functionally active as potent stimulators of T-cell proliferation. 3) Listeria treatment, as compared with standard inflammatory cytokine stimulation, does not promote the over-expression of inhibitory markers on moDCs. 4) Listeria treatment, as compared with standard inflammatory cytokine stimulation, does not potentiate the expansion of immune-dampening regulatory T-cells by moDCs. These findings confirm the immune-stimulatory properties of Listeria as a vaccine adjuvant. Studies of other DC subtypes are underway to identify the optimal DC for further study in Aims 2/3.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2012
- Accession Number
- ADA566789
Entities
People
- David J. Chung
Organizations
- Memorial Sloan Kettering Cancer Center