Advances in inducing adaptive immunity using cell-based cancer vaccines: Clinical applications in pancreatic cancer

Table 2 Clinical trials of dendritic cell-based cancer vaccines in pancreatic cancer patients

Cell-based cancer vaccines	Targets	Vaccines	Phase	Patients	Results	Ref.
Dendritic cells (DCs)	MUC1	DCs loaded with MUC1 peptide	Phase I/II	12 pancreatic or biliary cancer patients following surgical resection	These patients have been followed for more than 4 yr after vaccination, and 4 of them were alive without recurrence.	[46]
			Phase I	16 patients with pancreatic cancer	2 of 15 patients with resected PDA were alive and disease free at 32 and 61 mo.	[47]
			Phase I	7 patients with pancreatic cancer	These patients showed MUC1-specific immune responses; however, there was no significant clinical benefit.	[48]
		DCs transfected with MUC1 cDNA	Phase I/II	10 patients with pancreatic cancer	MUC1 specific immune responses were observed in 4 of 10 patients.	[49]
	WT1	DCs loaded with MHC class I restricted WT1 peptides	Retrospective analysis	49 patients with pancreatic cancer refractory to standard treatment	The median survival time from vaccines was 360 d. Erythema reaction at the vaccination site was a prognostic factor for a significant survival benefit.	[56]
		DCs loaded with MHC class I restricted WT1 peptides	Retrospective analysis	255 patients with pancreatic cancer refractory to standard treatment	The median survival time from diagnosis was 16.5 mo. Erythema reaction at the vaccination site was a prognostic factor for a significant survival benefit.	[60]
		DCs loaded with MHC class I restricted WT1 peptides	Phase I	10 patients with pancreatic cancer	The therapy was feasible, tolerable and effective in PDA patients without liver metastases.	[61]
		DCs loaded with MHC class I and class II restricted WT1 peptides	Phase I	7 patients with pancreatic cancer	WT1 peptide-specific delayed-type hypersensitivity (DTH) was detected in 4 of 7 patients with PDA vaccinated with DC/WT1-I/II and in 0 of 3 patients with PDA vaccinated with DC/WT1-I or DC/WT1-II. All 3 PDA patients with strong WT1-specific DTH reactions had a median OS of 717 d. A patient with multiple liver metastases has remained alive for over 1000 d and received more than 71 vaccinations.	[31,62,63]
	hTERT	DCs transfected with hTERT mRNA	Phase I	A patient who could not receive chemotherapy due to sever neutropenia	Vaccination was associated with induction of strong immune responses to multiple hTERT epitopes. The patient had been vaccinated with DC/hTERT mRNA alone for 3 yr and resulted in no evidence of active disease.	[66]
	CEA	DCs loaded with CEA mRNA	Phase I	3 patients with resected pancreatic cancer following neoadjuvant vaccine therapy	All 3 PDA patients showed injection site reactivity and remained alive without recurrence at more than 2.5 yr from the original diagnosis	[68]
	DCs transfected with an adenovirus encoding IL-12		Phase I	3 patients with pancreatic cancer	Intratumoral DC injections were guided by ultrasound. Vaccines induced a significantly increased infiltration of CD8+ T cells in some patients. A partial response was observed in 1 of 3 patients.	[73]
	penicillin-killed and lyophilized preparations of a low virulence strain (Su) of Streptococcus pyogenes (OK-432)-activated DCs and CD3-stimulated LAK cells		Phase I	5 patients with pancreatic cancer	Intratumoral injection of OK432-activated DCs, followed by intravenous infusion of CD3-stimulated LAK cells. One patient had a partial response and 2 had stable disease for over 6 mo. The median OS was 478 d.	[75]
Peripheral blood mononuclear cells (PBMCs)	K-ras	irradiated PBMCs were used as antigen-presenting cells and loaded with K-ras peptide	Phase I	9 patients with pancreatic cancer	Only one patient showed a positive cellular immune response. The worse prognosis of PDA patients on this immunization protocol using PBMCs as APCs may be associated with impaired induction of an antitumor immune responses.	[71]

MHC: Major histocompatibility complex; PDA: Pancreatic ductal adenocarcinoma; APC: Antigen-presenting cells; IL-12: Interleukin-12; WT1: Wilms’ tumor gene 1; MUC1: Mucin 1; hTERT: Human telomerase reverse transcriptase; CEA: Carcinoembryonic antigen.