Immune therapy for human papillomaviruses-related cancers

Table 1 Immune therapies for human papilloma virus-related lesions in clinical trials

Name	Target protein	Platform	Immune response/clinical efficacy	Ref.
Peptide-based
	E7	Synthetic peptides restricted to HLA-A2	T helper cell response, but no CTL response	[118,152]
HPV16-SLP	E6, E7	Synthetic overlapping long peptides	HPV-specific T cell response. Neither tumor regression nor prevention of progressive disease	[120-122]
Protein-based
L1VLPE7	E7	Chimeric L1-E7 VLP	Histological reduction to CIN 1 in 39% of treated patients compared to 35% of placebo recipients. This trend was not significant	[123]
SGN-00101	E7	Fusion protein of M. bovis Hsp and HPV 16 E7	Complete regression in 35% of patients with CIN 3	[125,126]
HPV16 E6/E7	E6, E7	Fusion protein of HPV 16 E6 and E7 proteins administered with the adjuvant ISCOMATRIX	Demonstrated important CD8+ T cell responses	[128]
TA-CIN	E6, E7, L2	Recombinant fusion protein consisting of E6, E7, and L2 from HPV	Imiquimod, for 8 wk, followed by 3 doses of TA-CIN induced complete regression in 32% of patients with VIN	[131]
DNA vaccine
pConE6E7	E6, E7	DNA vaccine that encodes a HPV 16 or 18 consensus E6/E7 fusion gene	Cellular immune response against HPV E6 and E7 antigens and protection against HPV E6 and E7-expressing tumors	[133,134]
ZYC101a	E7	Microencapsulated DNA vaccine encoding E7-specific CTL epitopes	In younger patients a 70% reduction of lesions was detected	[135]
Amolimogene	E6, E7	A poly (lactide co-glycolide) encapsulated plasmid DNA encoding T cell epitopes from HPV 16 and 18	Increase in HPV-specific T cells to epitopes from HPV 16, 18, 6 and 11. No correlation between cellular immunity and clinical response	[136]
Sig-E7(detox)-HSP70	E7	Fusion protein between HPV 16 E7 and heat shock protein 70	Low frequency and weak HPV E7-specific T-cell responses with no correlation to clinical results	[137]
Recombinant virus
TA-HPV	E6, E7	Vaccinia virus encoding modified HPV 16/18 E6 and E7 proteins	60% patients with high-grade VIN had partial reduction in lesion diameter, and an increase in lesion-infiltrating CD4+ and CD8+ T cells	[142,143]
TG4001	E6, E7	Vaccinia virus encoding modified HPV 16 E6 and E7 proteins, and the human IL-2	Ten patients (48%) with CIN 3 showed promising clinical responses at 6 mo, but no data on related immune response	[144]
MVA E2	E2	Vaccinia virus (MVA) encoding bovine papilloma virus (BPV) E2	19 out of 34 patients with high-grade CIN 3 lesions had complete regression. Specific cytotoxic activity against cancer cells correlated with clinical outcome	[113,114]
MVA-E1	E1	Vaccinia virus encoding the E1 sequence of HPV 16	MVA-E1 into C57BL/6 mice resulted in sustained HPV 16 E1-specific T cells with cytotoxic activity	[147]

HPV: Human papillomavirus; CTL: Cytotoxic T lymphocytes; VLP: Virus-like particles; VIN: Vulvar; CIN: Cervical intraepithelial neoplasia.