Virus-like antigen display for cancer vaccine development, what is the potential?

Vaccines containing whole viruses induce strong, protective humoral and cellular immune responses, whereas vaccines based on soluble proteins have generally shown poor efficacy. Virus-like particles (VLP) assembled from a single virus protein allow the display of a closely spaced, repetitive epitope pattern that mimics that of infectious agents and provide optimal stimulation of the mammalian immune system. However, the correct assembly of VLPs with large and complex proteins is challenging. The development of a simple modular system, based on highly reactive split-protein tag/catcher binding partners, enabled the high-density display of large proteins on the surface of non-enveloped icosahedral VLPs of bacteriophage origin. This versatile technology was used to develop a VLP vaccine displaying the whole extracellular domain of the human oncogene HER-2. In transgenic mice expressing human HER-2, the VLP vaccine induced strong antibody responses that protected the mice from the onset and growth of mammary carcinomas and inhibited in vitro human cell lines sensitive and resistant to the therapeutic monoclonal antibody trastuzumab. Such vaccines hold promise for integration in therapeutic regimes of breast cancer and other HER-2-positive human tumors.