Table 3.

Clinical trials of dendritic cells in cancer immunotherapy

DC	Tumor type	Combination therapy	Route, dose	Comparison (Medication group and control group)	Efficacy (partial response, PR; complete response, CR; overall survival, OS; progression-free survival, PFS)	Safety (grade III and IV adverse events)	Phase (I, II, III, n)	Trial registration	Ref.
CMV pp65 RNA-loaded DCs	Glioblastoma	CMV pp65-specific T cells		17 patients were randomized to receive CMV pp65-specific T cells with CMV-DC vaccination or saline	Increased in polyfunctional CMV-specific CD8+ T cells, correlated with overall survival		I (17)	NCT00693095	[110]
CMV pp65 mRNA pulsed DCs	Glioblastoma	DI-TMZ, GMCSF	DI-TMZ (100 mg/m2/d × 21 days per cycle), at least three DC vaccines, GM-CSF on day 23 ± 1 of each cycle.	Single arm	Median PFS and OS were 25.3 months and 41.1 months		I (11)	NCT00639639	[111]
hTERT-DCs	Acute myeloid leukemia		1 × 107 cells, 6 weekly injections, 6 biweekly injections	Single arm	Median follow-up of 52 months, 58% of patients in CR		II (36)	NCT00510133	[112]
DCs electroporated with Wilms' tumor 1 (WT1) mRNA	Acute myeloid leukemia		Intradermal injection of 0.5 × 1e6 WT1/DCs on the back of the patient	Single arm: 30 patients with AML at very high risk of relapse	5 year OS was higher in responders than in nonresponder patients. Age ≤ 65 and > 65, 5 year OS was 69.2% and 30.8%		II (30)	NCT00965224	[113]
HER2 peptide-pulsed DC1s	HERpos breast cancer			Patients were randomized for different injection routes	CR for ductal carcinoma in situ, invasive breast cancer patients was 28.6% and 8.3%	Well tolerated	I (54)	NCT02061332	[114]
Autologous tumor lysate plus DC	Metastatic colorectal cancer (mCRC)			52 patients were randomized to DC + best supportive care (BSC) vs. BSC	Median OS was 6.2 months in DC+BSC versus 4.7 months in BSC		III (52)	NCT01413295	[115]
DCs pulsed with killed PCa cells	Prostate cancer	Chemotherapy	Metronomic cyclophosphamide 50 mg p.o., DCVAC/PCa 1 × 107 dendritic cells per dose injected	Single arm: progressive metastatic castration-resistant prostate cancer	The median OS was 19 months		I/II (25)	CT 2009-017295-24	[116]
Autologous DCs pulsed with allogeneic tumor cell lysate	Mesothelioma		First, second and third cohort received 10, 25, 50 million monocyte-derived DCs per vaccination	9 patients divided over three different dose cohorts	Median PFS was 8.8 months	No dose limit	I (9)	NCT02395679	[117]
Autologous activated DCs	Lung cancer	Activated killer T cell AKT, chemoth., EGFR-TKI		Group A, immunotherapy; group B, chemotherapy.	The 2- and 5-year OS rates were 96.0 and 69.4% in group A and 64.7 and 45.1% in group B		III (103)	UMIN000007525	[118]
Activated DCs	Diverse solid tumors		Intratumorally injected at 2, 6, 15 million aDCs	Single arm	OS and TNFα levels increased		I (39)	NCT01882946	[119]
Tumor antigen-pulsed DCs	Hepatocellular carcinoma		Dendritic cell vaccines injected subcutaneously near to inguinal lymph nodes.	Single arm: patients with no viable tumor after primary treatments were included	9 patients had no tumor recurrence up to 24 weeks	Primary treatment for HCC.	I/IIa (9)	KCT0000427	[120]
Peptide-pulsed DCs	Pancreatic cancer (PC)	Toll-like receptor (TLR)-3 agonist poly-ICLC	Peptide-pulsed DC vaccines every 2 weeks. Concurrent intramuscular administration of Poly-ICLC	Single arm: 9 patients with metastatic PC, and 3 patients with locally advanced unresectable PC	Median overall survival was 7.7 months. One patient survived for 28 months		I (11)	NCT01410968	[121]
mRNA Electroporated DCs	Advanced melanoma	TriMixDC-MEL plus ipilimumab	Intradermally and intravenously plus ipilimumab every 3 weeks, then every 12 weeks	Single arm	6-month disease control rate was 51%, the overall tumor response rate was 38%		II (39)	NCT01302496	[122]
Ad-CCL21 Gene-Modified DCs	NSCLC	None	2 vaccinations by intratumoral injections	Single arm: stage IIIB/IV NSCLC	4/16 patients had stable disease at day 56. Median survival was 3.9 months		I (16)	NCT01574222	[123]
Autologous tumor lysate pulsed with DCs	Bone and soft tissue sarcoma		6 weekly DC injections into the inguinal or axillary region.	Single arm: metastatic or recurrent sarcomas	The 3-year overall and progression-free survival rates were 42.3% and 2.9%		I/II (37)		[124]
Autologous tumor cell pulsed Dcs (VAX-DC/MM)	Multiple myeloma	Monocyte-derived immature DCs	Intradermal VAX-DC/MM injection of 10 × 1e6 cells every week for 4 weeks	Single arm: relapsed or refractory MM	Most patients (77.8%) who received 10 × 1e6 cells showed an immunological response		I (12)	NCT02248402	[125]
None	High-risk stage III/IV melanoma	GM-CSF, multiepitope melanoma peptide		A multicenter intergroup randomized placebo-controlled trial	11.3% vs. 27.1% patients developed peptide-specific CD8+ T cell responses.		III (815)	NCT01989572	[126]