5T4 oncofoetal glycoprotein: an old target for a novel prostate cancer immunotherapy

Area of Science:

• Immunology
• Oncology
• Vaccinology

Background:

• The 5T4 antigen is a promising target for cancer immunotherapy.
• Existing immunisation platforms have shown limited success in eliciting 5T4-specific immune responses.

Purpose of the Study:

• To evaluate a heterologous prime-boost vaccination strategy using ChAdOx1 and modified vaccinia virus Ankara (MVA) expressing 5T4.
• To assess the immunogenicity, tumour protective efficacy, and potential for combination therapy with immune checkpoint inhibitors.

Main Methods:

• A heterologous prime-boost (ChAdOx1-MVA) and homologous (MVA) vaccination regimen was used in a mouse cancer model.
• Immune responses were analysed, focusing on CD8+ T cells.
• Tumour challenge studies were performed, with some groups receiving combination therapy with anti-PD-1, anti-PD-L1, or anti-LAG-3 monoclonal antibodies.

Main Results:

• The ChAdOx1-MVA vaccine induced strong, durable CD8+ T cell responses specific for 5T4.
• Homologous MVA vaccination failed to induce detectable 5T4-specific T cell responses.
• ChAdOx1-MVA vaccination provided complete protection against melanoma challenge, but showed modest efficacy in therapeutic settings.
• Combination therapy with anti-PD-1 monoclonal antibody significantly delayed tumour growth and improved survival in tumour-bearing mice.

Conclusions:

• The heterologous ChAdOx1-MVA prime-boost vaccination platform is effective in generating robust anti-tumour T cell immunity.
• Combining this vaccination strategy with PD-1 blockade offers a promising therapeutic approach for 5T4-positive cancers.
• This combinatorial approach warrants clinical translation for treating various solid tumours.