Virus‐like particles (VLPs) constitute a powerful and flexible platform that harness the immunogenicity of viruses without compromising on safety as VLPs cannot infect nor replicate due to the absence of the viral genetic material (DNA or RNA). The use of multivalent antigen display involving complex structures such as VLPs is one method of enhancing immune responses against weak immunogens. Antigen display on the surface of VLPs improves immunogenicity compared to soluble proteins.
In recent years, cancer immunotherapy with checkpoint inhibitors has achieved remarkable clinical outcomes in patients with advanced stages of cancer. Additionally, tumor-associated antigens and tumor-specific antigens provide an opportunity for tumor detection and destruction by the immune system. However, cancer cells have adopted several strategies to evade immune recognition, leading to a state of tumor tolerance. Biological response modifiers (such as vaccines) have the potential to fight cancer and can be used to break tumor tolerance. The vaccine must deliver a large number of selected cancer antigens to promote B cell and DC activation and antigen presentation to T cells. Antitumor immunity and local microenvironment can be strongly modulated by VLPs. With the VLP platform, it can target solid tumors or cancer stem cells (CSCs) with the potential to be used as prophylactic or therapeutic cancer vaccines, alone or in combination with chemotherapy, checkpoint inhibitors, or future therapies.
VLPs activate dendritic cells (DCs) through their interaction with pattern recognition receptors (PRRs). VLPs can attach and penetrate host cells because they conserve receptor binding sites. After immunization with VLP-based vaccines, VLP and adjuvant are recognized and internalized by DCs, inducing the release of pro-inflammatory cytokines to recruit more antigen-presenting cells (APCs) which later prompt an adaptive immune response. VLPs displaying antigenic epitopes or complete surface antigens can break B cell self-tolerance to induce therapeutic a tumor-specific B cell response.