Article

Dendritic cell vaccines in the treatment of multiple myeloma: advances and limitations.

Department of Internal Medicine-Hematooncology, Masaryk University Hospital, Jihlavska 20, 63900 Brno, Czech Republic.
Medical Oncology (impact factor: 2.14). 02/2002; 19(4):213-8. DOI:10.1385/MO:19:4:213 pp.213-8
Source: PubMed

ABSTRACT Dendritic cells (DCs) are antigen-presenting cells that play a key role in the induction of cytotoxic T-lymphocytes. Adjuvant immunotherapy with antigen-loaded DCs represents an attractive anticancer strategy for multiple myeloma (MM). Autologous DCs loaded with idiotypic protein or other myeloma-associated antigen have been used in several clinical trials. Preclinical and first clinical experience have provided valuable insights in the mechanisms of cellular immunity, but few, if any, patients with MM benefited from such vaccination. Taken together, the data suggest that antitumor T-cell responses fail in MM because of a deregulated cytokine network, downregulation of costimulatory surface receptor expression, and changes in T-cell repertoire, enabling tumor cells to escape immune effectors by preventing the antitumor immune response. We discuss current clinical protocols for DC-based immunotherapy in MM and review some strategies that may increase the efficacy of DC vaccines.

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    Article: Processing and presentation of exogenous HLA class I peptides by dendritic cells from human immunodeficiency virus type 1-infected persons.
    Xiao-Li Huang, Zheng Fan, Bonnie A Colleton, Rico Buchli, Hongyi Li, William H Hildebrand, Charles R Rinaldo
    [show abstract] [hide abstract]
    ABSTRACT: Dendritic cells (DCs) loaded with viral peptides are a potential form of immunotherapy of human immunodeficiency virus type 1 (HIV-1) infection. We show that DCs derived from blood monocytes of subjects with chronic HIV-1 infection on combination antiretroviral drug therapy have increases in expression of HLA, T-cell coreceptor, and T-cell activation molecules in response to the DC maturation factor CD40L comparable to those from uninfected persons. Mature DCs (mDCs) loaded with HLA A*0201-restricted viral peptides of the optimal length (9-mer) were more efficient at activating antiviral CD8(+) T cells than were immature DCs or peptide alone. Optimal presentation of these exogenous peptides required uptake and vesicular trafficking and was comparable in DCs derived from HIV-1-infected and uninfected persons. Furthermore, DCs from HIV-1-infected and uninfected persons had similar capacities to process viral peptides with C-terminal and N-terminal extensions through their proteasomal and cytosolic pathways, respectively. We conclude that DCs derived from HIV-1-infected persons have similar abilities to process exogenous peptides for presentation to CD8(+) T cells as those from uninfected persons. This conclusion supports the use of DCs loaded with synthetic peptides in immunotherapy of HIV-1 infection.
    Journal of Virology 04/2005; 79(5):3052-62. · 5.40 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

Adjuvant immunotherapy
 
antigen-loaded DCs
 
antitumor immune response
 
antitumor T-cell responses
 
attractive anticancer strategy
 
Autologous DCs
 
clinical trials
 
costimulatory surface receptor expression
 
current clinical protocols
 
DC vaccines
 
DC-based immunotherapy
 
DCs
 
Dendritic cells
 
deregulated cytokine network
 
first clinical experience
 
idiotypic protein
 
T-cell repertoire
 
tumor cells
 
vaccination
 
valuable insights
 

Tomas Büchler