Fusion of dendritic cells with multiple myeloma cells results in maturation and enhanced antigen presentation.
Dendritic cells (DCs) are potent antigen-presenting cells that are uniquely capable of inducing primary immune responses. Although tumour cells may directly inhibit DC maturation, exposure to tumour products may also result in their activation. Fusions of cancer cells and DCs are being explored as cancer vaccines. The effect of tumour cell fusion on DC maturation and their functional characteristics has not been defined. In the present study, immature and mature DC generated from human CD34+ and peripheral blood precursors were fused to multiple myeloma cells in the presence of polyethylene glycol. Fusion of both immature and mature DCs with tumour cells resulted in an activated phenotype. In this regard, fusion cells expressed interleukin-12, a cytokine essential for the induction of T-helper cell type 1 immunity. In contrast to immature DCs, fusion cells also strongly expressed CC-chemokine receptor R7, which is responsible for DC migration to draining lymph nodes. Fusions generated with both immature and mature DCs also potently stimulated T-cell expression of gamma-interferon and cytotoxic T lymphocyte killing of tumour targets. These findings demonstrate that tumour cell fusion induces DC maturation and the development of an activated phenotype necessary for their effectiveness as cancer vaccines.
Vasir
Baldev
B
Department of Medical Oncology and Dana-Farber/Harvard Cancer Center, Dana Farber Cancer Institute, Boston, MA 02115, USA. david_vasir@dfci.harvard.edu
Borges
Virginia
V
Wu
Zekui
Z
Grosman
Daren
D
Rosenblatt
Jacalyn
J
Irie
Masaki
M
Anderson
Kenneth
K
Kufe
Donald
D
Avigan
David
D
D017951:Antigen Presentation; D018952:Antigens, CD34 / Q000276:immunology; D019496:Cancer Vaccines; D002459:Cell Fusion; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000166:cytology*; D005434:Flow Cytometry; D006801:Humans; D006822:Hybrid Cells; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D009101:Multiple Myeloma / Q000276:immunology* / Q000473:pathology*; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D018952:Antigens, CD34; C515370:CCR7 protein, human; D019496:Cancer Vaccines; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma