Gene therapy in pancreatic cancer

Table 5 Closed clinical trials of gene therapy in pancreatic cancer

Trial ID and investigator	Phase	Clinical indication	Patients(n)	Transgenes	Vectors and target cells	Administration route	Combined therapy	Results
DE-0009 Löhr et al[67]	I/II	Inoperable PC	14	Cytochrome p450	Naked/plasmid DNA transfected allogeneic human 293 embryonic kidney cells	Inject into the tumor vasculature via supraselective angiography	In combination with low-dose ifosfamide	4 patients showed tumor regression, the other ten individuals remained stable. Median survival was doubled compared with historic controls. 1-yr survival rate was three times better
DE-0024 Pecher et al[207]	I/II	Advanced breast cancer, PC and gallbladder carcinoma	10 (2 PC)	MUC-1	Naked/plasmid DNA transfected autologus dendritic cells	Subcutaneous injection	None	9 patients showed signs of progression. Only one remained stable for 3 mo until she was transferred to another therapy. 3 of 10 patients developed vaccine-specific delayed-type hypersensitivity reaction (DTH). 4 of 10 patients showed increased mucinspecific INF-gamma- secreting CD8+ T cells
DE-0063 Kubuschok et al[208]	I	PC	3 healthy donors and 1 PC patient	Mutated ras oncoprotein	EB virus transformed autologous lymphoblastoid cells	Subcutaneous injection	None	All the subjects showed strong vaccine-induced muRas-specific cytotoxic T lymphocytes
DE-0083 Niethammer et al[209]	I	Advanced PC	45	VEGFR-2	Naked/plasmid DNA (oral DNA vaccine)	Oral administration	In combination with gemcitabine	Not reported
ES-0004 Mazzolini et al[210]	I	Liver cancer, PC, colorectal cancer	17 (3 PC)	Interleukin-12 (IL-12)	Adenovirus transfected autologous dendritic cells	Intratumoral injection	None	Treatment was well tolerated. 11 of 17 were assessable for response. A partial response was observed in 1 case with PC. Stable disease was observed in 2 patients and progression in 8 patients
FR-0018 Gilly et al[211]	I/II	Unresectable digestive cancer	6 (3 PC)	Interleukin-2 (IL-2)	Adenovirus	Intratumoral injection	None	Good safety. But final results of tumor responses were not reported
US-0853 Le et al[212]	I	Ovarian cancer, PC, lung cancer, mesothelioma	28	Mesothelin	Listeria monocytogenes	Intravenous injection	1: Live attenuated Listeria vaccine (n = 9); 2: live attenuated mesothein expressing Listeria vaccine ( n = 17)	In arm 2, Listeriolysin O and mesothelin-specific T-cell responses were seen and 37% of subjects lived ≥ 15 mo
US-0700 Galanis et al[213]	I	Gemcitabine-refractory, metastatic PC	12	Cyclin G1	Retrovirus	Intravenous injection	None	Good safety. But there was no evidence of anti-tumor activity
Kaufman et al[214]	I	Advanced PC	10	CEA, MUC-1, and TRICOM (including B7.1, ICAM-1, LFA-3)	Poxvirus	Subcutaneous injection	In combination with GM-CSF	Antigen-specific T-cell responses in 5 of 8 evaluated patients. 15.1 mo of median survival in responders vs 3.9 mo in non-responders. Overall median survival is 6.3 mo
Jaffee et al[141]	I	Resected PC	14	GM-CSF	Naked/plasmid DNA transfected allogeneic tumor cell vaccine	Intradermal injection	In combination with standard chemoradiation	3 of 14 patients developed DTH, and 3 patients had increased disease-free survival time (at least 25 mo after diagnosis)
US-0475 Lutz et al[215]	II	Resected PC	60	GM-CSF	Naked/plasmid DNA transfected allogeneic tumor cell vaccine	Intradermal injection	In combination with standard chemoradiation	The median disease-free survival is 17.3 mo with median survival of 24.8 mo. Induction of CD8+ mesothelin-specific T cells correlated with disease-free survival
Laheru et al[142]	A pilot study	Advanced PC	50	GM-CSF	Naked/plasmid DNA transfected allogeneic tumor cell vaccine	Intradermal injection	A: vaccine alone (n = 20) B: vaccine plus cyclophosphamide (n = 30)	Cohort B showed enhanced mesothelin-specific T-cell responses. Median survival values in cohort A and cohort B were 2.3 and 4.3 mo
Le et al[143]	Ib	Advanced PC	30	CM-CSF	Naked/plasmid DNA transfected allogeneic tumor cell vaccine	Intradermal injection	1: Ipilimumab alone (n = 15); 2: Ipilimumab plus vaccine (n = 15)	Median overall survival was 3.6 mo for arm 1 and 5.7 mo for arm 2. Mesothelin-specific T cells responses were associated with increased disease-free survival in arm 2