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 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.
Decker
William K
WK
Department of Blood and Marrow Transplantation, The University of Texas M.D. Anderson Cancer Center, Department of Blood and Marrow Transplantation, Box 65, 1515 Holcombe Blvd, Houston, TX 77030, USA. wkdecker@mdanderson.org
Xing
Dongxia
D
Li
Sufang
S
Robinson
Simon N
SN
Yang
Hong
H
Yao
Xin
X
Segall
Harry
H
McMannis
John D
JD
Komanduri
Krishna V
KV
Champlin
Richard E
RE
Shpall
Elizabeth J
EJ
D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D023201:CD40 Ligand / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D015470:Leukemia, Myeloid, Acute / Q000276:immunology*; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology; D012333:RNA, Messenger / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D000951:Antigens, Neoplasm; D012333:RNA, Messenger; D023201:CD40 Ligand; D007371:Interferon-gamma