Table 1.
Anti-human papillomavirus (HPV) therapeutic vaccines in clinical trials [31].
| Denomination | Description/Antigen | Adjuvant | Additional Treatment | Administration | Trial Design |
|---|---|---|---|---|---|
| TA-HPV [39] | Vaccinia Virus expressing E6 and E7 of HPV16 and 18 | surgical procedure radiation therapy |
i.m. injection | Phase II in patients with early CC | |
| TVGV-1 GPI-0100 Placebo [40] |
HPV16E7-PE (Pseudomonas exotoxin A); KDEL (ER retention signal) fusion protein | GPI-0100 (triterpene glycoside derived from saponins) | i.m. injection | Phase II randomized in double-blind patients with confirmed HPV-induced cervical HSIL | |
| HspE7/ Poly-ICLC [41] | HSP65 of Mycobacterium bovis and E7 HPV16 fusion protein | Poly-ICLC/synthetic complex of carboxy-methylcellulose, polyinosinic-polycytidylic acid, and poly-L-lysine double-stranded RNA | i.m. injection | Phase I/II in patients with CIN III | |
| Vvax001 [42] | Semliki Forest Virus vector encoding HPV-derived tumor antigens | Irradiated viral particles | i.m. injection | Phase I in patients with CIN 2, CIN 3, and CC | |
| INO-3112 (VGX3100 INO-9012) [43,44,45] |
DNA plasmids expressing E6 and E7 of HPV16 and 18 | IL-12 | Cisplatin; Radiotherapy; with or without Durvalumab (anti- PD-L1 mAb) | i.m. electroporation | Phase I/II in patients with CC, Head and Neck cancer; uterine cervical neoplasms |
| ISA101/ ISA101b [46] | 13 overlapping 25-35-mer peptides from HPV16 E6 and E7 proteins | Pegylated IFN-γ | Carboplatin and paclitaxel; bevacizumab (anti VEGF-A mAb) | i.m. injection | Phase I/II in patients with Advanced or Recurrent HPV16 CC |
| DPX-E7 vaccine [47] | HPV16 E7-specific CTL peptide delivered by proprietary liposome formulation | i.m. injection | Phase I/II in HLA-A02 patients with head and Neck cancer, CC, Cancer of anus | ||
| PepCan [48,49] | 4 HPV16-E6 peptides escalation doses | Candida albicans extract (Candin®) | i.d. injection | Phase I/II in women with HSIL | |
| ADXS11-001 [50] | HPV 16 E7 fused to non-hemolytic listeriolysin O protein | i.m. injection | Phase II in patients with persistent, recurrent SCC or non-SCC | ||
| VB10.16 vaccine [51] | DNA expressing HPV16 E6-E7, a dimerization domain and an APC targeting domain | needle-free injection | Phase I/II in patients with CIN 2 | ||
| GX-188E [52] Placebo |
DNA expressing the E6/E7 fusion protein of HPV16 and 18, plus Flt3L and tPA sequences signals | Pembrolizumab (anti-PD1 mAb) | i.m. electroporation | Phase II randomized, double-blind, multi-center in patients with CIN II and CIN III | |
| NGVL4a-Sig/E7(detox)/HSP70 [53] | Vaccinia virus expressing E6/E7; DNA plasmid encoding signal peptide, a detox form of HPV-16 E7 and the HSP70 | Imiquimod | i.m. injection | Phase I in patients with HPV- precancerous lesions and CC | |
| GX-188E GX-I7 [54] |
DNA E6/E7 fusion proteins of HPV16 and 18 plus GX-I7 | GX-I7 (IL-7 and hybrid Fc) | Imiquimod | i.m. electroporation | Phase 1 in patients HPV-positive |
| pNGVL4a-CRT/E7-Detox DNA Vaccine [55] | DNA HPV16 E7detox linked to calreticulin (CRT) | Cyclophosphamide intravenously up to 24 h | i.m. electroporation | Phase I in patients with Head and Neck Cancer | |
| Ad-E6E7 MG1-E6E7 [56,57] |
Adenovirus expressing E6 and E7 plus Oncolytic Maraba virus expressing E6 and E7 | Atezolizumab (anti-PD-L1 mAb) | i.m. | Phase I |
Abbreviations: CC (cervical cancer); HSIL (high grade intraepithelial cervical lesion); PE (Pseudomonas aeruginosa exotoxin A); CIN II and CIN III (cervical intraepithelial neoplasia of grade II and III); SCC (squamous cell carcinoma), APC (antigen presenting cell), Flt3L (Fms-like tyrosine kinase-3 ligand), tPA (tissue-type plasminogen activator), HSP (heat shock protein); CTL (cytotoxic T lymphocyte), i.m. (intra muscular), i.d. (intra dermal) injection.