Pancreatic cancer vaccine: a unique potential therapy

Figures & data

Table 1 Strategies to modulate tumor microenvironment

Target	Models	Strategies	References
CD40	Preclinical and clinical (both PDA)	Agonist monoclonal Ab to CD40 in combination with gemcitabine	59,110
CSF-IR	Preclinical (glioma) and clinical (breast ca)	Monoclonal Ab to CSF-1R (BLZ945)	65
CCR2	Preclinical (breast)	Monoclonal Ab to CCL2	62,63
GM-CSF	Preclinical (transplantable PDA)	Short hairpin RNA for GM-CSF or monoclonal Ab to GM-CSF	66,68
Monocytes	Preclinical (fibrosarcoma, ovarian, Lewis lung ca)	Trabectedin	III
Ly6G	Preclinical (PDA)	Monoclonal Ab to Ly6G (1A8)	67
CXCL12	Preclinical (PDA)	Monoclonal Ab to CXCL4 (AMD3100)	70
Smoothened	Preclinical and clinical (PDA)	IPI-926, semisynthetic derivative of cyclopamine, and genetic ablation	71,73
α-SMA	Preclinical (PDA)	Genetical ablation of a-SMA+ cells	72

Abbreviations: PDA, pancreatic ductal adenocarcinoma; RNA, ribonucleic acid; GM-CSF, granulocyte and monocyte-colony stimulating factor; Ab, antibody; ca, cancer; α-SMA, alpha-smooth muscle actin.

Table 2 Clinical trials consisting in vaccine strategies^a

Number	Status	Intervention	Phase
NCT00836407	Completed	Allogeneic PDA cells transfected with GM-CSF + ipilimumab	I
NCT01088789	Recruiting	Allogeneic PDA cells transfected with GM-CSF given long term ± cyclophosphamide	II
NCT01896869	Recruiting	Allogeneic PDA cells transfected with GM-CSF + ipilimumab in patients receiving FOLFIRINOX	II
NCT00727441	Active, not recruiting	GVAX + cyclophosphamide	NS
NCT00389610	Active, not recruiting	GVAX after surgery	II
NCT00569387	Both completed	Algenpantucel-L after surgery	II
NCT00614601
NCT00305760	Completed	GVAX + cituximab/cyclophosphamide	II
NCT02451982	Not yet recruiting	GVAX + cyclophosphamide ± nivolumab	I/II
NCT00084383	Completed	GVAX + chemotherapy after surgery	II
NCT01595321	Active, not recruiting	Allogeneic PDA cells transfected with GM-CSF + cyclophosphamide + stereotactic body radiation + FOLFIRINOX	I
NCT00683085	Terminated	HLA-A02 restricted peptide from VEGF-R + gemcitabine	I/II
NCT00425360	Completed	GM-CSF + peptide from telomerase + capecitabine or gemcitabine	III
NCT00837135	Withdrawn	GI-4000 (ras peptide containing different mutated sites) ± T-cell adoptive transfer	I
NCT00655785	Completed	Peptides derived from VEGF-RI and R2 + gemcitabine	I/II
NCT00868114	Active, not recruiting	KLH-pulsed autologous dendritic cell vaccine in combination with TNFerade or radiation	II
NCT02465983	Recruiting	CART antimesothelin + CART anti-CDI9	I

Note:

a For complete review see ClinicalTrials.gov.

Abbreviations: PDA, pancreatic ductal adenocarcinoma; GM-CSF, granulocyte and monocyte-colony stimulating factor; FOLFIRINOX, 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin; NS, not specified; VEGF-R, vascular endothelial growth factor-receptor; KLH, keyhole limphet hemocyanin.

Figure 1 Conventional and future therapies for PDA.

Notes: At present, conventional therapies include surgery for resectable patients and chemo- and/or radiotherapy for locally advance and metastatic PDA. Preclinical and clinical data demonstrate that immunotherapy can be efficiently combined with conventional therapies to improve the survival of patient with PDA. Immunotherapies include whole cell, loaded-DC, peptide, or DNA vaccines in combination with antibodies to modulate stroma and immune responses. All these can be combined with chemo- and/or radiotherapy in neoadjuvant settings to shrink tumors to render them resectable, or after surgical resection to avoid recurrence.
Abbreviations: PDA, pancreatic ductal adenocarcinoma; DC, dendritic cell.