Tumors are recognized by the immune system, but tumors that reach clinically relevant size have established mechanisms to suppress the immune response and protect themselves from immune attack. One approach to enable effective immune response is to change the immunosuppressive tumor microenvironment into an immunostimulatory environment by introducing immunostimulatory reagents directly into tumors. This is essentially an antitumor therapeutic “in situ vaccination”, because the tumors provide the antigens and the adjuvants are the immunostimulatory reagents. The overall goal of the approach is to not only stimulate an anti-tumor immune response against the directly treated tumor, but more importantly to stimulate a systemic anti-tumor response to treat unseen metastases. There are many immunostimulatory reagents that can be used and each has different capabilities. Here we report on plant-derived viral-like nanoparticles from Cowpea Mosaic Virus used in mouse cancer models. These particles are only composed of viral capsid proteins, have no nucleic acids and have no recognized immunostimulatory reagents. However, they are strongly immunostimulatory through unknown pathways and cause dramatic changes in the tumor microenvironment that lead to primary tumor reduction and resistance to metastatic tumors. The treatment is immune-mediated since it requires IFN-γ, IL-12, and adaptive immunity and also involves neutrophils. Tumor reduction or elimination occurs in many anatomic locations and with multiple tumor types. Most importantly, treatment of a primary tumor by direct intratumoral injection mediates robust rejection of a rechallenge with the same tumor. The mechanisms and pathways of immunostimulation are under investigation. In addition to the inherent immunostimulatory adjuvant properties of these nanoparticles, they are a versatile platform to which other reagents for immune modulation can be attached. This demonstration of the value of viral-like nanoparticles for treatment of cancer opens a new avenue of cancer immunotherapy.
Citation Format: Patrick Lizotte, Amy Wen, NIcole Steinmetz, Steven Fiering. Viral-like nanoparticles for tumor immunotherapy by in situ vaccination mediate potent antitumor immunity. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr A140.
- ©2016 American Association for Cancer Research.