Table 1.

Promising Immunotherapies in HNSCC

Drug	Mechanism	Phase of development in human cancer	HNSCC development
TA-specific monoclonal antibodies
Cetuximab	Anti-EGFR chimeric IgG1 mAb	FDA approved in HNSCC, colon cancer	FDA approved
Panitumumab	Anti-EGFR IgG2 humanized mAb	II/III	II/III
Nimotuzumab	Anti-EGFR IgG1 humanized mAb	II	II
Onartuzumab	Anti-cMet IgG1 single-arm humanized mAb	II/III	NA
AV-203	Anti-HER3 IgG1 humanized mAb	I	I
MM-121	Anti-HER3 IgG2 humanized mAb	I/II	NA
Cixutumumab	Anti-IGFR IgG1 humanized mAb	II	II
Enhancing ADCC to TA-specific mAb
IL-12	Cytokine agonist of NK cell activation	II	II
VTX-2337	TLR 8 agonist; enhanced DC activation and IL-12 secretion	II	I/II
Restoring STAT1/STAT3 signaling balance
Ruxolitinib	JAK 1 and JAK 2 inhibitor	I/II/III	NA
SAR302503	Selective JAK 2 inhibitor	II	NA
BMS911543	Selective JAK 2 inhibitor	I/II	NA
Pegylated IFN-γ	Upregulation of pSTAT1	NA; phase III in chronic hepatitis C	NA
Targeting immunosuppressive cytokines
Bevacizumab	Anti-VEGF IgG1 humanized mAb	FDA approved in lung, colon cancers	III
Ficlatuzumab	Anti-HGF IgG1 humanized mAb	I/II	I
AMG 102	Anti-HGF IgG2 humanized mAb	I/II	NA
Siltuximab	Anti-IL-6 IgG1 humanized mAb	I/II	NA
T cell checkpoint inhibitors
Ipilimumab	Anti-CTLA4 IgG1 humanized mAb	FDA approved in melanoma	I
Tremelimumab	Anti-CTLA4 IgG2 humanized mAb	III	NA
BMS-936558	Anti-PD-1 IgG4 humanized mAb	I–III	NA
BMS-936559	Anti-PD-L1 IgG4 humanized mAb	I	NA
Therapeutic cancer vaccines
HPV 16 E6 and E7 peptide vaccine	Long peptide vaccine with incomplete freund’s adjuvant	I	NA
MAGE-3 and HPV-16 vaccine	Trojan construct peptide vaccine	I	I
HPV pNGVL4a-CRT/E7 (Detox) DNA vaccine	Detoxified E7 DNA in a pNGVL4a plasmid backbone	I	I
TG4001 vaccine	Modified vaccinia virus expressing E6 and E7 oncoproteins	I	NA
Lm-LLO-E7 vaccine	Live-attenuated Listeria monocytogenes bacterium vaccine which secretes HPV-16 E7 antigen fused to listeriolysin O	I	I
Multi-epitope p53 vaccine	Wild type peptide/autologous dendritic cell vaccine	I	I