Plant virus-like particle-based cancer immunotherapy

N.F. Steinmetz, S. Fiering, P. Lizotte, A.M. Wen
Case Western Reserve University,
United States

Keywords: nanoparticles, virus-like particles, cancer, immunotherapy, in situ vaccination

Summary:

Plant virus-like particle-based cancer immunotherapy Nicole F. Steinmetz1,2,3,4, Steven Fiering5, Patrick Lizotte5, Amy M. Wen1 Departments of 1Biomedical Engineering, 2Radiology, 3Materials Science and Engineering, 4Macromolecular Science and Engineering, Case Western Reserve University, and 5Norris Cotton Cancer Center Geisel School of Medicine at Dartmouth Email: nicole.steinmetz@case.edu The current interest in tumor immunotherapy is intense, and growing rapidly. This is because it has been scientifically and clinically shown that the immune system has the potential to destroy undetected metastases. Our approach is focused on a cancer immunotherapy strategy termed “in situ vaccination:” we have introduced virus-like particles (VLPs) into tumor microenvironments in mice and demonstrated potent immune-mediated anti-tumor effects in the setting of lung metastatic and flank tumors. The VLPs are proteinaceous nanoparticles produced through molecular farming in plants. They lack viral nucleic acids and are non-infectious (toward mammals or plants). We use a plant VLP as a novel immunotherapy and do not co-deliver cancer-specific epitopes. This in situ vaccination depends on the antigens in the tumor itself, and therefore can be regarded as a personalized medicine. We show that VLPs from cowpea mosaic virus are a potent immunotherapeutic that stimulates immune-mediated anti-tumor effects if introduced into the tumor environment after tumors are established. We demonstrate efficacy in the setting of localized and metastatic melanoma, breast cancer, ovarian cancer, and colon cancer. Perhaps most importantly, our data indicates that this immune-stimulation is able to generate an immune memory that prevents tumor progression, metastasis, and recurrence. Prevention of relapse and cancer development, even before physicians are able to detect its onset, represents a vertical leap in the field. [Nature Nanotechnology, in press.]