Anti-HPV type 16 Monoclonal antibody, Clone DBNWJS-2

Immunotherapy utilizing induced pluripotent stem cell (iPSC) technology has great potential. Functionally rejuvenated cytotoxic T lymphocytes (CTLs) can survive long-term as young memory T cells in vivo, with continuous tumor eradication. Banking of iPSCs as an unlimited "off-the-shelf" source of therapeutic T cells may be feasible. To generate safer iPSCs, we reprogrammed human papilloma virus type 16 (HPV16) E6-specific CTLs by Sendai virus vector without cotransduction of SV40 large T antigen. The iPSCs efficiently differentiated into HPV16-specific rejuvenated CTLs that demonstrated robust cytotoxicity against cervical cancer. The tumor-suppressive effect of rejuvenated CTLs was stronger and more persistent than that of original peripheral blood CTLs. These rejuvenated HPV16-specific CTLs provide a sustained tumor-suppressive effect even for epithelial cancers and constitute promising immunotherapy for cervical cancer.

Anogenital and oropharyngeal cancers caused by human papillomavirus (HPV) infections account for 4.5% of all cancer cases worldwide. So far, only the initial infection with selected high-risk types can be prevented by prophylactic vaccination. Already existing persistent HPV infections, however, can currently only be treated by surgical removal of resulting lesions. Therapeutic HPV vaccination, promoting cell-based anti-HPV immunity, would be ideal to eliminate and protect against HPV-induced lesions and tumors. A multitude of vaccination approaches has been tested to date, many of which led to high amounts of HPV-specific T cellsin vivo. However, growing evidence suggests that not the induction of systemic but of local immunity is paramount for tackling mucosal infections and tumors. Therefore, recent therapeutic vaccination studies have focused on how to induce tissue-resident T cells in the anogenital and oropharyngeal mucosa. These approaches include direct mucosal vaccinations and influencing the migration of systemic T cells toward the mucosa. The efficacy of these new vaccination approaches is best testedin vivoby utilizing orthotopic tumor models, i.e. HPV-positive tumors being located in the animal's mucosa. In line with this, we here review existing HPV tumor models and describe two novel tumorigenic cell lines for the MHC-humanized mouse model A2.DR1. These were used for the establishment of an HPV16 E6/E7-positive vaginal tumor model, suitable for testing therapeutic vaccines containing HLA-A2-restricted HPV16-derived epitopes. The newly developed MHC-humanized orthotopic HPV16-positive tumor model is likely to improve the translatability ofin vivofindings to the clinical setting.