Double loading of dendritic cell MHC class I and MHC class II with an AML antigen repertoire enhances correlates of T-cell immunity in vitro via amplification of T-cell help

Therapeutic vaccination with dendritic cells presenting tumor-specific antigens is now recognized as an important investigational therapy for the treatment of neoplastic disease. Dendritic cell cross-presentation is credited with the ability of tumor lysate-loaded dendritic cells to prime both CD4 a...

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Bibliographic Details
Published in:Vaccine 2006-04, Vol.24 (16), p.3203-3216
Main Authors: Decker, William K., Xing, Dongxia, Li, Sufang, Robinson, Simon N., Yang, Hong, Yao, Xin, Segall, Harry, McMannis, John D., Komanduri, Krishna V., Champlin, Richard E., Shpall, Elizabeth J.
Format: Article
Language:English
Subjects:
AML
Antigens
Antigens, Neoplasm - immunology
Antigens, Neoplasm - metabolism
Applied microbiology
Biological and medical sciences
CD40 Ligand - immunology
CD8-Positive T-Lymphocytes - immunology
Cells, Cultured
Clinical trials
Cytotoxicity, Immunologic
Dendritic Cells
Dendritic Cells - immunology
Flow cytometry
Fundamental and applied biological sciences. Psychology
Humans
Immune system
Immunologic Memory
Immunotherapy
Interferon-gamma - biosynthesis
Leukemia, Myeloid, Acute - immunology
Lymphocyte Activation
Lymphocyte Subsets - immunology
Microbiology
Mortality
Patients
R&D
Research & development
RNA, Messenger - immunology
RNA, Messenger - metabolism
T cell receptors
T-cell Help
T-Lymphocytes - immunology
Transplants & implants
Vaccination
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
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Summary:Therapeutic vaccination with dendritic cells presenting tumor-specific antigens is now recognized as an important investigational therapy for the treatment of neoplastic disease. Dendritic cell cross-presentation is credited with the ability of tumor lysate-loaded dendritic cells to prime both CD4 and CD8-specific T-lymphocyte responses, enabling the generation of cancer specific CTL activity without the loading of the classical MHC class I compartment. Recently, however, several reports have raised doubts as to the efficiency of cross-presentation as a mechanism for CTL priming in vivo. To examine this issue, we have doubly-loaded human dendritic cells with both AML-specific tumor lysate and AML-specific tumor mRNA. Our results show that these doubly-loaded dendritic cells can mediate superior primary, recall, and effector lytic responses in vitro in comparison to those of dendritic cells loaded with either tumor lysate or tumor mRNA alone. Enhanced recall responses appeared to be influenced by CD40/CD40L signaling, underscoring the importance of T-cell help in the generation and perpetuation of the adaptive immune response.
ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2006.01.029