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PROTAXE6-(E7)2
- Development stage
- Preclinical
- Lead developer
- University of Michigan
- Modality
- Peptides, PROTACs (E3 ligase recruitment) → Targeted Protein Degraders (TPDs) → Small Molecules, Bivalent/Multivalent Binders → Multivalent & Scaffold-Based Small Molecules → Small Molecules, Vaccines & Immunotherapeutics
01
Overview
PROTAXE6-(E7)2 is a trivalent proteolysis-targeting vaccine (PROTAX) designed for the treatment of HPV-16-associated malignancies, such as head and neck squamous cell carcinoma (HNSCC). Developed by researchers at the University of Michigan, the PROTAX platform utilizes peptide antigens conjugated to an E3 ligase-binding ligand via chemical linkers. Upon entering antigen-presenting cells (APCs), the PROTAX molecule recruits E3 ligases to ubiquitinate the linked antigens (specifically HPV-16 E6 and E7), facilitating their rapid proteolytic processing by the proteasome. This mechanism significantly enhances antigen cross-presentation on MHC class I molecules to CD8+ T cells compared to traditional peptide vaccines. PROTAXE6-(E7)2 is HLA-A02:01-restricted and has demonstrated the ability to expand tri-specific CD8+ T cell responses and increase the production of interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) in patient-derived samples.
- Other names
- PROTAX-E6-(E7)2
02
Targets
CRL4-CRBN (Cereblon-based E3 ubiquitin ligase complex)HPV16 E6 oncoproteinHPV16 E7 (Human papillomavirus 16 E7 protein)
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