Immunotherapy for pancreatic cancer

Table 1 Potential immunotherapeutic agents for pancreatic cancer

Immunotherapeutics	Mechanisms		FDA approval
Ipilimumab	Antagonist antibody to CTLA-4 on T cells	CTLA-4: Suppressing the initiation of immune response	Other cancers
Pembrolizumab, nivolumab, cemiplimab	Antagonist antibody to PD-1 on T cells	PD-1: Suppressing the antitumor response of Tc cell	Yes1
Atezolizumab, durvalumab, avelumab	Antagonist antibody to PD-L1 on cancer cell or MDSC	PD-L1: A ligand of PD-1, promoting PD-1 signaling	Other cancers
Imiquimod	Agonist of TLR7 on MDSC or M2 macrophage	TLR7: Promoting macrophage polarization towards an M1 phenotype	Other cancers
Plerixafor (AMD3100), BL-8040	Antagonist of CXCR4 on T cells	CXCR4: Receptor of CXCL12, negatively regulating Tc cell immune function	Other cancers
Indoximod	Antagonist of IDO in MDSC or APC	IDO: Inducing tolerance to tumor-derived antigens in APC and inhibiting Tc cell	-
Imidazole-dioxolane	Antagonist of HO in M2 macrophage	HO: Suppressing Tc cell by producing carbon monoxide	-
APX005M, CP-870893	Agonist antibody to CD40 on APC, T cell, or M1 macrophage	CD40: Proinflammatory action	-
CAR T cells	Directly targeting cancer cells via reprogramming a patient's own T cells with a CAR that recognizes a specific antigen	Potential targets in pancreatic cancers: CEA, mesothelin, ROR1, EpCAM, HER2, MUC1	Other cancers
Cancer vaccines	Activating T cell via presentation by APC	GVAX2, GV1001 (telomerase peptide vaccine)	Other cancers

¹All solid tumors with microsatellite instability.

²Allogeneic irradiated whole-cell tumor vaccine transfected with granulocyte-macrophage colony-stimulating factor gene. CTLA-4: Cytotoxic T lymphocyte-associated protein 4; PD-1: Programmed cell death 1; PD-L1: Programmed cell death ligand 1; TLR7: Toll-like receptor 7; MDSC: Myeloid-derived suppressor cell; CXCR4: C-X-C chemokine receptor type 4 or CD184; CXCL12: C-X-C motif chemokine 12; IDO: Indoleamine 2,3-dioxygenase; HO: Heme oxygenase; Tc cell: Cytotoxoc T cell; APC: Antigen presenting cell; CAR: Chimeric antigen receptor; ROR1: Receptor tyrosine kinase-like orphan receptor 1; EpCAM: Epithelial cell adhesion molecule; HER2: Human epidermal growth factor receptor 2; MUC1: Mucin 1; FDA: United States Food and Drug Administration; CEA: Carcinoembryonic antigen; GVAX: Granulocyte-macrophage colony-stimulating factor-transfected pancreatic tumor vaccine.