Plant-derived viral-like nanoparticle immunotherapy suppresses development of metastatic lung cancer (TUM10P.1058)

Abstract

Abstract Conventional chemo- and radiotherapy are largely ineffective for metastatic melanoma and emerging immune checkpoint inhibitors, while promising, remain ineffective in the majority of patients and carry associated autoimmune side effects. We hypothesized that treatment of lung tumor-bearing mice with a viral-like nanoparticle could modulate the lung immune environment and prevent the development of B16F10 metastatic-like lesions. We report here that inhalation of a self-assembling viral-like particle derived from the cowpea mosaic virus (CPMV) suppresses the development of tumors in the lungs of intravenous challenged mice. The disparity in tumor burden between CPMV- and PBS-treated mice was pronounced, and the effect was immune-mediated as it was not seen in Ifn-γ-/-, Il-12-/-, and NOD/scid/Il2Rγ-/- mice. CPMV nanoparticles were rapidly taken up by antigen-presenting cells that had trafficked to the lung following treatment and resulted in their activation and cytokine/chemokine production. CPMV particles are manufactured in plants and purified of nucleic acids and therefore are nonreplicative and free of endotoxin and other pattern recognition receptor agonists. CPMV nanoparticles are highly scalable, stable, nontoxic, and modifiable with drugs and antigens. These properties, combined with their inherent immunogenicity and significant efficacy against a poorly immunogenic tumor, present CPMV as an attractive novel immunotherapy against cancer metastatic to the lung.