Table 3 Clinical trials of dendritic cells in cancer immunotherapy

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

HER^pos 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]