Pancreatic cancer: Update on immunotherapies and algenpantucel-L

Figures & data

Table 1. Mechanisms of action of vaccine strategies in pancreatic cancer.

Vaccine type	Mechanism of Action	Notable Examples
Whole cell vaccines	Irradiated tumor cells that express single or multiple TAAs	• Algenpantucel-L^27: 2 PC cell lines engineered to express αGal, a naturally immunogenic epitope. Through epitope spreading, immune response spreads to include common PC-associated antigens. • GVAX^43,47: 2 PC cell lines engineered to express GM-CSF, a cytokine that promotes activation of DCs.
Peptide and protein vaccines	Peptide or protein commonly expressed by PCs.	• RAS-based vaccines^48-55 • Telomerase-based vaccines (e.g. GV1001)^58,59 • VEGFR2-based vaccines^64, 65 • Survivin-based vaccines^67 • Gastrin-based vaccines^70 • HSP-peptide complex-based vaccines^72
Dendritic cell (DC) vaccines	DCs engineered to express specific TAA ex vivo	• MUC-1-pulsed DCs^73 • DC-based vaccine plus LAK cells^78 • DCs loaded with CEA-encoding mRNA^79
Vaccines with microorganisms	Naturally immunogenic viral or bacterial vectors, which are engineered to express TAAs	• CRS-207^47: live-attenuated strain of Listeria monocytogenes (Lm) that encodes mesothelin, a commonly expressed pancreatic TAA • IMM101^80,81: heat-killed whole cell vaccine of Mycobacterium obuense

Abbreviations: PC, pancreatic cancer; TAAs, tumor associated antigens.

Figure 1. Proposed mechanism of action of algenpantucel-L immunotherapy. Algenpantucel-L relies on preexisting anti-αGal antibody response; vaccine cells are destroyed by complement-mediated lysis, which results in cross-presentation of tumor antigens; tumor specific CD8+ cytotoxic T cells are generated which recognize patient's own tumor; humoral immunity relies on antitumor antibodies.

Table 2. NLG0205 algenpantucel-L phase II study summary and correlations with immunological biomarker response.

	Overall evaluable	Anti-MSLNAb response		Anti-CALR Ab response		Any one Ab response anti-MSLN, anti-CEA, anti-αGal	More than one Ab response anti-MSLN, anti-CEA, anti-αGal
Endpoint	n = 69	Yesn = 20	Non = 44	Yesn = 31	Non = 33	Yesn = 26	Non = 27	Yesn = 13
Median OS(months)	24.1	42	20	35.8	19.2	26	17	>36 (NR)
3-year OS	39%	50%	32%	55%	21%	42%	19%	69%

Abbreviations: Ab, antibody; MSLN, mesothelin; CALR, calreticulin; αGal, α-galactosyl epitopes,

NR, not reached.

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