Immunotherapy Targeting HPV16/18 Generates Potent Immune Responses in HPV-Associated Head and Neck Cancer

Area of Science:

• Immunology
• Oncology
• Vaccine Technology

Background:

• Programmed death (PD-1) receptor-directed antibodies show limited clinical response rates in advanced head and neck squamous cell cancer (HNSCCa).
• Viral neoantigens, such as HPV16/18 E6/E7 proteins, present potential targets for therapeutic immunization.
• Therapeutic immunization may complement PD-1 inhibition strategies in HNSCCa.

Purpose of the Study:

• To evaluate the safety, tolerability, and immunogenicity of MEDI0457, a DNA immunotherapy targeting HPV16/18 E6/E7 with IL12 encoding plasmids, delivered via electroporation.
• To assess the immune response generated by MEDI0457 in patients with locally advanced, p16-positive HNSCCa.

Main Methods:

• Phase Ib/II clinical trial involving 22 patients with locally advanced, p16-positive HNSCCa.
• MEDI0457 administered via electroporation using the CELLECTRA device.
• Immunogenicity assessed by IFNγ ELISpot, T-cell activity, CD8+/FoxP3+ ratio, and immune infiltrates in tumor samples.

Main Results:

• MEDI0457 demonstrated a favorable safety profile with mild injection site reactions and no grade 3-5 adverse events.
• Eighteen of 21 evaluable patients exhibited elevated antigen-specific T-cell activity, with persistent responses up to 1 year.
• Induction of HPV-specific CD8+ T cells and increased perforin+ immune infiltrates were observed. One patient achieved a complete response with subsequent anti-PD-1 therapy.

Conclusions:

• MEDI0457 effectively generates durable HPV16/18 antigen-specific peripheral and tumor immune responses.
• This immunotherapy approach shows potential as a complementary strategy to PD-1/PD-L1 inhibition in HPV-associated HNSCCa.
• Further investigation is warranted to improve therapeutic outcomes in HPV-associated HNSCCa.