Table 2.

Summary of selected clinical trials of cancer vaccine and immunotherapy with cohorts of pancreatic cancer patients.

Vaccine Type		Investigator	Phase	Stage	Therapy	Clinical and Immunological Outcomes
Immune checkpoint inhibitors	CTLA-4	Royal (2010)	II	27 patients with locally advanced PDA	Ipilimumab	No responders by response evaluation criteria.
		Brahmer (2012)	I	14 patients with advanced PDA	Nivolumab	No objective responses were observed.
		Segal (2014)/NCT01693562	I/II	10–20 patients with PDA	MEDI4736	Anti-tumor activity was preliminarily reported for some PDA patients at the 2014 ASCO annual meeting.
Therapeutic vaccines	Whole cell vaccines	Jaffee (2001)	I	14 patients with resected PDA	GM-CSF vaccine (GVAX) with chemoradiotherapy	3 patients developed DTH and remained disease-free for greater than 10 years.
		Lutz (2011)	II	60 patients with resected PDA	GM-CSF vaccine (GVAX) with chemoradiotherapy (5FU)	Median disease-free survival was 17.3 months and median overall survival was 24.8 months. Vaccine induced mesothelin-specific CD8+ T cell responses were observed in HLA-A1+ and HLA-A2+ patients, which correlated with DFS.
		Laheru (2008)	II	50 patients with advanced PDA	GM-CSF vaccine (GVAX) with cyclophosphamide (Cy)	Median survival in patients given Cy 1 day before vaccine was 4.3 months (2.3 months without Cy). Mesothelin-specific CD8+ T cell responses in HLA class I patients were enhanced with Cy.
		Lutz (2014)	pilot	54 patients with resected PDA	GM-CSF vaccine (GVAX) with cyclophosphamide (Cy)	Vaccine-induced intratumoral tertiary lymphoid aggregates were observed. Enhanced survival and mesothelin-specific T cell responses were observed in patients with a suppressed Treg pathway and an enhanced Th17 pathway. Upregulation of PD-1 and PD-L1 in the tumor was observed after vaccination.
		Hardacre (2013)	II	70 patients with resected PDA	Algenpantucel-L with 5-FU and gemcitabine	Disease-free survival was 62% at 1 year. Overall survival was 86% at 1 year.
	Antigen-specific vaccines	Gjertsen (1996)	I/II	5 patients with histologically confirmed PDA	Mutated Kras peptide	2 patients with an immune response showed longer survival.
		Gjertsen (2001)	I/II	48 patients, 10 with surgically resected PDA and 38 with advanced PDA	Mutated Kras peptide with GM-CSF	Peptide specific immunity was induced in 58% of evaluable patients. Active CD4+ T cells specific for mutant Kras were found in the tumor post-vaccination. Patients with advanced PDA were able to develop an immune response to the peptide vaccine, which correlated with prolonged survival (median survival was 148 days in responders compared to 61 days in non-responders).
		Abou-Alfa (2011)	I	24 patients with resected PDA	Mutated Kras peptide	Median recurrence free survival was 8.6 months, while median overall survival was 20.3 months. Only 1 patient (11%) had detectable immune responses specific to the patient’s Kras mutation, which was assessed as a DTH. 3 patients (13%) displayed non-specific DTH responses.
		Le (2012)	I	7 patients with PDA	CRS-207	Vaccine-induced immune responses against listeria were observed in 3 of 7 PDA patients who had an overall survival of ≥15 months. Induction of mesothelin-specific immune responses did not correlate with overall survival in this small study.
Combinatori al immunother apy		Le (2013)	Ib	15 previously treated patients with advanced PDA	Ipilimumab + GM-CSF vaccine (GVAX)	Median overall survival was 5.7 months and 1 year overall survival was 27%. Patients with an overall survival > 4.3 months had an increase in mesothelin-specific T cells and enhancement of the T cell repertoire.
		Le (2015b)	II	61 previously treated patients with advanced PDA	GM-CSF vaccine (GVAX) with cyclophosphamide (Cy) + CRS-207	Median overall survival was 9.7 months. An increase in mesothelin-specific CD8+ T cell responses were observed at 20 weeks. Robust mesothelin-specific CD8+ T cell responses was associated with longer overall survival.