PROTACE6

PROTACE6 is a proteolysis-targeting chimera (PROTAC) designed to degrade the human papillomavirus (HPV) E6 oncoprotein. It is composed of a nanobody (A5) that targets HPV16 E6 protein, fused to the Von Hippel-Lindau protein (VHL), which recruits the CRL2VHL E3 ligase for E6 degradation. The drug is delivered via a clinically viable DNA vaccine, offering advantages such as localized expression and low production costs. Preclinical studies in an immunocompetent mouse model of HPV+ cancer demonstrated that intralesional administration of PROTACE6 reduced tumor burden by inhibiting E6's oncogenic function and stimulating host immune responses, including CD4+ and CD8+ T cells. This approach represents a novel targeted therapy for HPV-related cancers, such as cervical cancer.