Table 1.

Recent clinical trials using different sources of dendritic cells and varying maturation strategies.

Maturation regimen	DC phenotype	Description: cancer type, stage, sample size and antigen used	Important findings	Ref.
Immature DCs
GM-CSF and IL-4	Immature	Normal, healthy volunteers being vaccinated against influenza n = 2 DCs pulsed with influenza antigens and KLH	Antigen-specific immune suppression Inhibition of pre-existing antigen-specific T-cell function	[87]
GM-CSF and IL-4	Immature	Recurrence of a variety of pediatric tumors including neuroblastoma, Ewing’s sarcoma, other sarcomas and renal malignancies n = 15 DCs pulsed with tumor lysate and KLH	Antigen-specific T-cell sensitization Inconclusive, although overall favorable clinical results Significant regression of multiple metastatic sites was seen in one patient	[271]
Mature versus immature DCs
GM-CSF and IL-4 IL-1β, TNF-α, IL-6, PGE2	Immature Mature	Stage IV cutaneous melanoma and progressive disease n = 11 DCs pulsed with HLA-specific melanoma class I peptide	Mature DCs demonstrated increased CD4+ T-cell recall Mature DCs induced increased antigen-specific CTLs No definitive clinical conclusions	[272]
pDCs
No human clinical trials
MoDCs
IL-1β, TNF-α, IL-6, PGE2	Mature	Metastatic melanoma n = 28 DCs pulsed with MHC class I and class II peptides	Immune-specific T-cell sensitization Th1-polarized immune response detectable in all patients Mixed, although encouraging clinical results with one patient experiencing full tumor regression	[273]
IL-1β, TNF-α, IL-6, PGE2	Mature	Surgically resected pancreatic or biliary tree (gallbladder, ampullary or bile duct) cancer n = 12 DCs pulsed with MLJC1 peptide	No direct measure of antigen-specific T-cell sensitization No measurable antibody response Overall increase of Foxp3 expressing regulatory CD4+ cells Mixed clinical outcomes, some evidence of improved survival	[274]
IL-1β, TNF-α, IL-6, PGE2	Mature	Metastatic renal-cell carcinoma n = 14 DCs pulsed with autologous tumor lysate and KLH or DCs pulsed with peptide antigen	Immune-specific T-cell sensitization No objective clinical response	[275]
TNF-α,IL-6, IL-1β, PGE2	Mature	Stage I multiple myeloma patients n = 9 DCs were pulsed with autologous Id protein tumor antigen	Antigen-specific T-cell sensitization Unable to clearly assess clinical response	[276]
TNF-α, IL-1β, PGE2	Mature	Patients with newly diagnosed GBM n = 8 DCs pulsed with autologous tumor lysate and combination radiation and chemotherapy	Mixed immunogenicity, overall increased antigen-specific response Inconclusive clinical outcomes	[277]
TNF-α, IL-6, IL-1β, PGE2	Mature	Patients with progressive malignant melanoma without brain metastases n = 28 DCs pulsed with peptides and/or autologous and allogeneic tumor lysates depending on HLA-A2 status administered in conjunction with IL-2 and metronomic cyclophosphamide	Antigen-specific T-cell sensitization No decrease in Treg cells No objective clinical response, but evidence of improved disease stabilization	[278]
IFN-α, TNF-α, polyinosinic:polycytidylic acid	DC1	Metastatic patients with a variety cancers n = 24 DCs pulsed with autologous tumor lysates combined with cyclophosphamide, Peg-IFN and GM-CSF	Four of 11 patients demonstrated antigen-specific T-cell activation Circulating tumor cells decreased in six of 19 patients 21% disease stabilization but overall equivocal clinical outcomes	[279]
IL-1, TNF, IFN and poly-l:C	DC1	Glioblastoma patients n = 22 DC pulsed with previously identified HLA-A2-restricted peptide epitopes	Induced increased systemic production of Th1 cytokines Mixed results for antigen-specific sensitization 9% clinical response	[280]
LPS and IFN-γ	DC1	Her2-positive DCIS patients n = 27 DCs pulsed with HLA-A2-restricted peptide epitopes	Antigen-specific T-cell sensitization Reduced or eliminated Her2 expression 90% clinical response	[157,213]
MoDCs and LCs
CD40L or inflammatory cytokines: IL-1 b, IL-6, TNF-α, andPGE2	DC1	Stage III/IV melanoma patients n = 36 Compared LC pulsed with melanoma antigen with MoDCs pulsed with melanoma peptide antigen (tyrosinase, gp100)	LCs demonstrated increased antigen-specific sensitization and were less dependent on exogenous IL-15 No significant difference in overall efficacy	[79]
CD34+ hematopoietic-derived DCs (includes LCs and interstitial DCs)
GM-CSF, FLT3-L, TNF	Not specified	Metastatic melanoma n = 18 DC pulsed with epitopes to melanoma peptide antigens (tyrosinase, gp 100 and Mart-1)	Antigen-specific T-cell sensitization Overall enhanced immune response Unable to determine clinical benefit	[281]
Interstitial DCs
No human clinical trials

These trials demonstrate a bias towards use of monocyte-derived DCs, matured with inflammatory cytokines in an attempt to elicit a DC1-driven immune response.

CTL: Cytotoxic T lymphocyte; DC: Dendritic cell; DCIS: Ductal carcinoma in situ; GBM: Glioblastoma multiforme; GM-CSF: Granulocyte-macrophage colony stimulating factor; KLH: Keyhole limpet hemocyanine;

LC: Langerhans cell; LPS: Lipopolysaccharide; MoDC: Monocyte-derived dendritic cell; pDC: Plasmacytoid DC; Peg-IFN: Pegylated interferon.