Cationic nanogel–based nasal therapeutic HPV vaccine prevents the development of cervical cancer
Menée à l'aide de modèles murins, cette étude met en évidence l'intérêt d'un vaccin thérapeutique, administré par voie intranasale et comportant un nanogel cationique avec antigène E7 du papillomavirus humain de type 16, pour empêcher le développement d'un cancer du col de l'utérus
Therapeutic vaccines against cervical cancer caused by human papillomavirus (HPV) are still an unmet medical need, despite a prophylactic HPV vaccine being available, and the now-licensed systemic vaccines may have a limited effect on the reproductive tract. To specifically inhibit cervical cancer development, the concept of mucosal immunity based on the reproductive-respiratory axis was adopted to develop a nasal HPV therapeutic vaccine. We used a cationic nanogel for the nasal vaccine delivery system and targeted HPV16 E7, an oncoprotein in HPV-driven cervical cancer to demonstrate the feasibility of a nasal therapeutic vaccine. The vaccine was combined with cyclic di–adenosine monophosphate as a cell-mediated immunity-inducing adjuvant. Intranasal immunization with the nanogel vaccine induced E7-specific CD4+ and CD8+ T cells in mouse cervicovaginal tissue. An antitumor effect due to the infiltration of vaccine-induced E7-specific T cells was also observed in an orthotopic tumor model in mice. Furthermore, intranasal immunization of nonhuman primates with the nanogel vaccine using a spray device that is also applicable to humans induced E7-specific T cells in the reproductive tissues. Our findings demonstrated that this nasal therapeutic vaccine effectively controlled cervical cancer and will contribute to preclinical evidence for clinical testing in the near future. Cationic nanogel–based nasal therapeutic vaccine induces cancer-specific immune responses and inhibits cancer development in cervical tissue. Human papillomavirus (HPV) can cause cervical cancer, and although prophylactic HPV vaccines exist, they do not control or affect preexisting HPV infections and HPV-associated cancers. To address this, Nakahashi-Ouchida et al. developed a cationic nanogel for nasal vaccine delivery of an HPV16 E7–targeted vaccine. They show efficacy in mice at controlling cervical cancer and induction of T cells in mouse cervicovaginal tissue. In addition, they show intranasal immunization of nonhuman primates and induction of T cells in cervical tissue, which supports clinical translation that requires further study. —Dorothy Hallberg
Science Translational Medicine , résumé, 2025