Table 1.
Study | Patient Population/Stage of Disease | Vaccine | Immunologic Analysis | Median Survival | Reference | |
---|---|---|---|---|---|---|
Peptide Vaccines | Gjertsen, 1995 | 5 patients with histologically confirmed PDA | Mutated KRAS Peptide | 2/5 with vaccine-induced ras specific CD4+ and CD8+ T cells | 2 immune responders showed longer survival | [39] |
Gjertsen, 2001 | 48 patients, 10 surgically resected PDA & 38 with advanced PDA | Mutated KRAS Peptide with GM-CSF | Mutant KRAS specific response in 58% of patients | 148 days in responders versus 61 days in non- responders | [43] | |
Bernhardt, 2006 | 48 patients with unresectable PDA | Telomerase Peptide (GV1001) with GM-CSF | Immune response measured as DTH and in vitro T cell proliferation in 24 of 38 patients (75% of intermediate dose group) | 8.6 months in intermediate dose group | [46] | |
Gilliam, 2012 | 154 patients with advanced PDA, unwilling or unable to take chemotherapy | Gastrin peptide vaccine (G17DT) versus placebo | Anti-G17DT response in 78% of patients in G17DT arm | 151 days (G17DT) vs. 82 days (placebo), P= 0.03 | [44] | |
Recombinant Vaccines | Kaufman, 2007 | 10 patients with advanced stage PDA | TRICOM, MUC-1 & CEA in poxvirus with GM-CSF | Antigen specific T cell responses in 5 of 8 evaluated patients | 15.1 months in responders vs. 3.9 months in non-responders (p=0.002), 6.3 months overall | [49] |
Le, 2012 | 28 patients with mesothelioma, lung, pancreatic, or ovarian cancer liver metastases | Live attenuated Listeria vaccine (ANZ-100) (n=9) vs. Live attenuated mesothelin expressing Listeria vaccine (CRS-207) (n=17) | LLO and Mesothelin specific T cell responses seen in CRS-207 arm | 37% of patients in CRS-207 arm alive after 15 months | [30] | |
Dendritic Cell Vaccine | Lepisto, 2008 | 12 patients with resected pancreatic and biliary cancers | MUC-1 pulsed autologous DC vaccine | Not reported | 26 months | [56] |
Whole Cell Vaccines | Jaffee, 2001 | 14 patients with resected PDA | GM-CSF secreting whole cell vaccine in combination with standard chemoradiation | 3 of 14 patients developed DTH to autologous tumor cells | NR (3 of 14 patients with prolonged disease free survival) | [61] |
Laheru, 2008 | 50 patients with advanced PDA, having failed at least 2 chemotherapy regimens | Arm A: GM-CSF whole cell vaccine alone (n=20) vs. Arm B: GM-CSF whole cell vaccine & Cy (n=30) | Enhanced mesothelin specific T cell responses associated in Arm B | Arm A: 2.3 months Arm B: 4.3 months | [63] | |
Hardacre, 2010 | 62 patients with resected PDA | HyperAcute-Pancreas Vaccine plus standard gemcitabine/5-FU based chemotherapy | NR | NR | [66] | |
Lutz, 2011 | 60 patients with resected PDA | GM-CSF secreting whole cell vaccine in combination with standard chemoradiation | Induction of CD8+ mesothelin specific T cells correlating with overall survival | 24.8 months | [62] | |
Combinatorial Immunotherapy | Le, 2012 | 30 patients with locally advanced, treatment refractory or metastatic PDA | Ipilimumab (IPI) alone vs. IPI plus GM-CSF whole cell vaccine | IRAEs (p=0.037), mesothelin T cell responses (p=0.012), and enhancement of the T cell repertoire (p=0.026) associated with OS in both arms | IPI alone: 3.3 months IPI plus GM-CSF vaccine: 5.5 months | [71] |
PDA pancreatic ductal adenocarcinoma; vs. versus; DTH delayed type hypersensitivity responses; GM-CSF granulocyte macrophage colony stimulating factor; DC dendritic cell; LAK lymphokine activated killer; Cy cyclophosphamide; LLO listeriolysin o; OS overall survival; IRAE immune related adverse effects