Trial watch: Dendritic cell-based anticancer therapy.
The use of patient-derived dendritic cells (DCs) as a means to elicit therapeutically relevant immune responses in cancer patients has been extensively investigated throughout the past decade. In this context, DCs are generally expanded, exposed to autologous tumor cell lysates or loaded with specific tumor-associated antigens (TAAs), and then reintroduced into patients, often in combination with one or more immunostimulatory agents. As an alternative, TAAs are targeted to DCsin vivoby means of monoclonal antibodies, carbohydrate moieties or viral vectors specific for DC receptors. All these approaches have been shown to (re)activate tumor-specific immune responses in mice, often mediating robust therapeutic effects. In 2010, the first DC-based preparation (sipuleucel-T, also known as Provenge®) has been approved by the US Food and Drug Administration (FDA) for use in humans. Reflecting the central position occupied by DCs in the regulation of immunological tolerance and adaptive immunity, the interest in harnessing them for the development of novel immunotherapeutic anticancer regimens remains high. Here, we summarize recent advances in the preclinical and clinical development of DC-based anticancer therapeutics.
Gustave Roussy Cancer Campus ; Villejuif, France ; INSERM , U1138; Paris France ; Equipe 11 labellisée par la Ligue Nationale contre le Cancer; Centre de Recherche des Cordeliers ; Paris France ; Université Paris-Sud/Paris XI ; Orsay, France.
Norma
N
Bloy
Gustave Roussy Cancer Campus ; Villejuif, France ; INSERM , U1138; Paris France ; Equipe 11 labellisée par la Ligue Nationale contre le Cancer; Centre de Recherche des Cordeliers ; Paris France.
Jonathan
J
Pol
Gustave Roussy Cancer Campus ; Villejuif, France ; INSERM , U1138; Paris France ; Equipe 11 labellisée par la Ligue Nationale contre le Cancer; Centre de Recherche des Cordeliers ; Paris France.
Fernando
F
Aranda
Gustave Roussy Cancer Campus ; Villejuif, France.
Alexander
A
Eggermont
INSERM , U1138; Paris France ; Equipe 13; Centre de Recherche des Cordeliers ; Paris France ; Université Pierre et Marie Curie/Paris VI ; Paris France.
Isabelle
I
Cremer
INSERM , U1138; Paris France ; Equipe 13; Centre de Recherche des Cordeliers ; Paris France ; Université Pierre et Marie Curie/Paris VI ; Paris France.
Wolf Hervé
WH
Fridman
Department of Immunology; 2nd Medical School Charles University and University Hospital Motol ; Prague, Czech Republic ; Sotio a.s. ; Prague, Czech Republic.
Jitka
J
Fučíková
INSERM , U1138; Paris France ; Université Pierre et Marie Curie/Paris VI ; Paris France ; Laboratory of Integrative Cancer Immunology; Centre de Recherche des Cordeliers ; Paris France ; Université Paris Descartes/Paris V; Sorbonne Paris Cité ; Paris France.
Jérôme
J
Galon
Université Paris Descartes/Paris V; Sorbonne Paris Cité ; Paris France ; INSERM , U970; Paris France ; Pôle de Biologie; Hôpital Européen Georges Pompidou, AP-HP ; Paris France.
Eric
E
Tartour
Department of Immunology; 2nd Medical School Charles University and University Hospital Motol ; Prague, Czech Republic ; Sotio a.s. ; Prague, Czech Republic.
Radek
R
Spisek
Department of Medicine; Immunobiology and Yale Cancer Center; Yale University ; New Haven, CT USA.
Madhav V
MV
Dhodapkar
Gustave Roussy Cancer Campus ; Villejuif, France ; INSERM, U1015, CICBT507 ; Villejuif, France.
Laurence
L
Zitvogel
INSERM , U1138; Paris France ; Equipe 11 labellisée par la Ligue Nationale contre le Cancer; Centre de Recherche des Cordeliers ; Paris France ; Université Paris Descartes/Paris V; Sorbonne Paris Cité ; Paris France ; Pôle de Biologie; Hôpital Européen Georges Pompidou, AP-HP ; Paris France ; Metabolomics and Cell Biology Platforms; Gustave Roussy Cancer Campus ; Villejuif, France.
Guido
G
Kroemer
Gustave Roussy Cancer Campus ; Villejuif, France ; INSERM , U1138; Paris France ; Equipe 11 labellisée par la Ligue Nationale contre le Cancer; Centre de Recherche des Cordeliers ; Paris France ; Université Paris Descartes/Paris V; Sorbonne Paris Cité ; Paris France.
Lorenzo
L
Galluzzi
DC, dendritic cell; DC-based vaccination; FDA, Food and Drug Administration; IFN, interferon; MRC1, mannose receptor, C type 1; MUC1, mucin 1; TAA, tumor-associated antigen; TLR, Toll-like receptor; Toll-like receptor agonists; Treg, regulatory T cell; WT1, Wilms tumor 1; antigen cross-presentation; autophagy; iDC, immature DC; immunogenic cell death; mDC, mature DC; pDC, plasmacytoid DC; regulatory T cells