A HPV therapeutic vaccine candidate : Procervix
HPV 16 and HPV 18 are the 2 most dangerous HPV types world-wide. Taken together, HPV 16 and/or HPV 18 are found in 52% of high grade squamous cell lesions , 70% of squamous cell carcinoma (Clifford, Franceschi et al. 2006), and 85% of adenocarcinoma (Bosch, Burchell et al. 2008). That is why Genticel decided to provide a therapeutic solution for HPV 16+ and/or 18+ patients.
ProCervix is a first-in-class bivalent HPV therapeutic vaccine candidate currently evaluated in a large Phase I clinical trial for women who are infected with HPV 16 and/or HPV 18, before appearance of cervical lesions. It’s the first vaccine to address the medical needs of this high-risk population.
Interim phase I results indicate good safety and local tolerance at the highest dose evaluated. Antigen-specific T cell responses have been detected in a majority of vaccinated women. Moreover, viral clearance is several-fold higher in the group of patients treated with ProCervix than in the placebo group.
About therapeutic vaccines
Therapeutic vaccines differ from preventive vaccines by their ability to fight an infectious or malignant disease already established in patients. Generally this is possible thanks to induction of cell-mediated immunity rather than antibody- and complement-mediated immunity. This characteristic helps the patient to eliminate infected or otherwise affected abnormal cells.
Cell-mediated immunity is mediated by specific immune-competent cells, which are activated when they encounter their target antigen. Such cells include macrophages, natural killer cells (NK) and T cells. There are many different types of T cells, of which at least two are very important for an effective immune response: antigen-specific cytotoxic CD8+ killer T cells and CD4+ helper T cells. Similarly to the humoral immune response where certain ‘B’ cells are responsible for memory, cell-mediated immunity will induce specialized ‘T’ cells to “remember” the antigen (memory T cells). ProCervix induces both killer and helper T cells against the target antigens HPV16-E7 and HPV18-E7 because the vaccine contains two vector CyaA proteins carrying respectively E7 antigen of HPV 16 and of HPV 18, named CyaA HPV 16-E7∆ and CyaA HPV 18-E7∆.
Mode of action of CyaA- based therapeutic vaccines
Relevant reviews on therapeutic vaccines against cancer and infectious diseases are given by
- Ha S-J., West E., Araki K., Smith K. and Ahmed R. (2008) Manipulating both the inhibitory and stimulatory immune system towards the success of therapeutic vaccination against chronic viral infections. Immunological reviews 223: 317- 333.
- Huh WK, Roden RB. The future of vaccines for cervical cancer. Gynecol Oncol 2008; 109: S48-S56.
- Hung CF, Ma B, Monie A, Tsen SW, Wu TC. Therapeutic human papillomavirus vaccines: current clinical trials and future directions. Expert Opin Biol Ther 2008; 8: 421-39. Free full text
- Trimble CL, Frazer IH. Development of therapeutic HPV vaccines. Lancet Oncol 2009; 10: 975-80. Free full text
- Ward S. and Dalgleish A. (2007) Editiorial - Therapeutic cancer vaccines. Vaccine 25S, B1 – B3.