In-situ vaccination of plant virus destroyed cancer tumors while triggering natural immune response

12/29/2015 - 15:14


The shells of a common plant virus, inhaled into a lung tumor or injected into ovarian, colon or breast tumors, not only triggered the immune system in mice to wipe out the tumors, but provided systemic protection against metastases, researchers from Case Western Reserve University and Dartmouth University report.

The scientists tested a 100-year-old idea called in-situ vaccination. The idea is to put something inside a tumor and disrupt the environment that suppresses the immune system, thus allowing the natural defense system to attack the malignancy.

READ MORE ON CASE WESTERN RESERVE UNIVERSITY | THINK

Ref: In situ vaccination with cowpea mosaic virus nanoparticles suppresses metastatic cancer. Nature Nanotechnology (2015) | DOI: 10.1038/nnano.2015.292

ABSTRACT

Nanotechnology has tremendous potential to contribute to cancer immunotherapy. The ‘in situ vaccination’ immunotherapy strategy directly manipulates identified tumours to overcome local tumour-mediated immunosuppression and subsequently stimulates systemic antitumour immunity to treat metastases. We show that inhalation of self-assembling virus-like nanoparticles from cowpea mosaic virus (CPMV) reduces established B16F10 lung melanoma and simultaneously generates potent systemic antitumour immunity against poorly immunogenic B16F10 in the skin. Full efficacy required Il-12, Ifn-γ, adaptive immunity and neutrophils. Inhaled CPMV nanoparticles were rapidly taken up by and activated neutrophils in the tumour microenvironment as an important part of the antitumour immune response. CPMV also exhibited clear treatment efficacy and systemic antitumour immunity in ovarian, colon, and breast tumour models in multiple anatomic locations. CPMV nanoparticles are stable, nontoxic, modifiable with drugs and antigens, and their nanomanufacture is highly scalable. These properties, combined with their inherent immunogenicity and demonstrated efficacy against a poorly immunogenic tumour, make CPMV an attractive and novel immunotherapy against metastatic cancer.