Type of study DCs source Pulse antigen Verification model Results References

 

 

 

 

 

No. Year
In vitro PB of patients with PDAC CA 19-9 Cytotoxicity in co-culture with pancreatic cancer cells Higher cytotoxic activity against pancreatic cancer cells using CA 19-9 pulsed DCs [165] 2000
In vitro PB of blood donors Pancreatic cancer cell lines lysates Cytotoxicity in co-culture with pancreatic cancer cells Higher cytotoxic activity against pancreatic cancer cells using pulsed DCs [166] 2001
In vitro PB or buffy coats of blood donors Lysates of apoptotic and non apoptotic pancreatic cancer cell lines Cytotoxicity in co-culture with pancreatic cancer cells Higher cytotoxic activity against pancreatic cancer cells using DCs pulsed with apoptotic pancreatic cancer cell lysates [167] 2002
In vivo animal model Syrian hamster BM Pancreatic cancer cell lines lysates Hamsters inoculated s.c. with a piece of tumor and treated with s.c. injection of unpulsed or pulsed DCs Inhibition of tumor growth in hamsters treated with pulsed DCs [168] 2002
Human study Autologous PB monocytes mRNA encoding CEA Three patients with resected PDAC following neoadjuvant chemoradiotherapy received DCs monthly for 6 months All three alive without evidence of disease more than 2.5 yr from the original diagnosis [169] 2002
Human study Autologous PB monocytes Autologous tumor cell lysate for 10 vaccinations and lysate of the tumor cell lines AsPc-1 and BxPc-3 for a further five vaccinations. One patient with stage IV PDAC given pulsed DCs in three-week intervals injected into a growing lymph node for a total of fifteen vaccinations Stable disease for six months [170] 2003
In vivo animal model Syngenic BM RNA derived from a pancreatic cancer cell line Intratumor injections of DCs in orthotopic PDAC DCs administration induced significant antitumor immunity and significantly reduced tumor volume [171] 2003
In vivo animal model Syngenic BM Heat-treated tumor lysate (HTL-DC) and tumor lysate (TL-DC) from a pancreatic cancer cell line Immunocompetent C57BL/6 mice inoculated s.c. with PANC02 cells at −18 day. At day 0, 7, and 15, s.c. immunization The group treated with HTL-DC had significantly smaller tumors at 30 days [172] 2006
In vivo animal model Syngenic BM Alpha-galactosylceramide Immunocompetent C57BL/6 mice inoculated s.c. with PANC02 cells. At day 0, 14, and 28, s.c. immunization Pulsed DCs strongly decreased tumor growth and increased the percentage of tumor-free mice [173] 2006
In vivo animal model Syngenic BM Panc02 cells Immunocompetent C57BL/6 mice inoculated s.c. with PANC02 cells. Mice received either no treatment, Panc02-pulsed DCs, gemcitabine (Gem) or Panc02-pulsed DCs plus Gem DC-based vaccination alone was almost as equally effective as Gem treatment in preventing death. Survival could be significantly increased in the combined treatment arm [174] 2007
Human study Autologous PB mononuclear cells Unpulsed Seven patients unsuccessfully treated (Gem) for unresectable PDAC received intratumoral injection of 10 billion or more immature DCs Safety: unpulsed DCs delivered into the pancreatic cancer using endoscopic ultrasound-guided fine needle injection is safe [175] 2007
Human study Autologous PB mononuclear cells MUC1 peptide 20 pts with stage III – IV PDAC received 2 to 15 times intradermal injection of pulsed DCs One patient with multiple lung metastases had a complete response. Five patients had stable disease. The long survival group (more than 6 months) showed significantly higher expression of mature DC (CD83+) [176] 2008
Human study Autologous PB mononuclear cells OK432 (a penicillin-killed and lyophilized preparation of a low-virulence strain of Streptococcus pyogenes) 5 non metastatic inoperable PDAC treated with Gem and with endoscopic ultrasound-guided fine needle injection of OK432-pulsed DC 1 patient had partial response and 2 were long-standing survivors (more than 6 months). Induction of tumor antigen-specific CTLs [177] 2009
Human study Autologous PB mononuclear cells Autologous tumor cell lysate 12 patients with advanced disease treated with Gem and DCs injected intradermally next to an inguinal lymph node. Patients were treated in bi-weekly intervals for the first 6 weeks, then once every 4 weeks 1 patient had a partial remission, 2 had stable disease, and 5 survived 1year or more after diagnosis of advanced disease [178] 2011
Human study Autologous PB mononuclear cells MUC1 7 patients with recurrent lesions or metastasis after surgery underwent intradermal vaccinations at 2 week intervals Safety: DCs is non-toxic and capable of inducing immunological response to tumor antigen MUC1 in advanced. pancreatic cancer patients. The vaccination did not prolong patients’ survival time or stabilize their disease [179] 2012
Human study Autologous PB mononuclear cells None 9 PDAC received (DC group) while 15 PDAC did not received  (non-DC group), preoperative endoscopic ultrasound-guided tumor inoculation of  iDCs and OK432 Two DC group patients, one of whom was stage IV with distant lymph node metastasis, survived more than 5 years without requiring adjuvant therapy [180] 2012
In vivo animal model Syngenic BM None Mice received Panc02 cells s.c. and were treated with PBS, Gem alone, DCs alone, or combination therapy with DCs and Gem Gem therapy alone delayed tumor growth. Combined therapy with Gem and DC vaccination delayed tumor growth, this combination leading to significantly prolonged survival in Panc02-bearing mice [181] 2013
Human study Autologous PB mononuclear cells CA 19-9 Retrospective analysis of 134 patients subjected to long antigen exposition DCs therapy Median survival was significantly higher in group of patients who started immunotherapy within 2 months of diagnosis  or repeated immunotherapy [182] 2013
In vivo animal model Syngenic BM OVA protein Mice were implanted with orthotopic PancOVA tumors and treated with combinations of DC-OVA i.p. and/or Gem Mice treated with OVA-DC showed highly efficient tumor control, 9/13 mice having complete remission leading to long-term survival of more than 150 days [183] 2014
Human study Autologous PB mononuclear cells WT1 and/or MUC1 peptide antigens according to patient’s HLA-A type 255 patients were injected 5 or more times intradermally with DCs in close proximity to axial and/or inguinal lymph nodes, biweekly. 12 patients received DC vaccines simultaneouswith first-line chemotherapy; the other 243 patients began receiving DC vaccines after first- or second-line chemotherapy Erythema after vaccination > 3 cm was an independent and treatment-related prognostic factor for better survival [184] 2014
Table 2: Dendritic cells (DCs) vaccination strategy. Precursor DCs obtained from peripheral blood (PB) or bone marrow (BM) were pulsed with different tumor derived antigens before testing their ability to activate anti tumor T cell based cytotoxicity or their effects on tumor growth and disease prognosis. In vitro, in vivo animal models and human studies are reported.