Plant Virus Nanoparticles Combat Cancer

Viral nanoparticles (VNPs) are self-assembled nanometric complexes whose size and shape are similar to those of the virus from which they are derived. VNPs are arousing great attention due to potential biotechnological applications in fields like nanomedicine and nanotechnology because they allow the presentation of polypeptides of choice linked to the virus structural proteins. Starting from tobacco etch virus (TEV), a plant plusstrand RNA virus that belongs to the genus Potyvirus (family Potyviridae), here we describe the development of recombinant hybrid VNPs in Nicotiana benthamiana plants able of exposing simultaneously different proteins on their surface. This system is based on the synergic coinfection of TEV and potato virus X (PVX; Potexvirus), in which PVX provides a second TEV CP in trans allowing a mixed assembly. We first generated genetically modified hybrid VNPs simultaneously displaying green and red fluorescent proteins on their surface. A population of decorated and nondecorated CPs resulting from the insertion of the picornavirus F2A ribosomal escape peptide was required for viral particle assembly. Correct assembly of the recombinant mosaic VNPs presenting the exogenous peptides was successfully observed by immunoelectron microscopy. We next achieved the production of hybrid VNPs expressing a nanobody against SARS-CoV-2 and a fluorescent reporter protein, whose functionality was demonstrated by ELISA and dot-blot assay. Finally, we engineered the production of hybrid multivalent VNPs carrying two different nanobodies against distinct epitopes of the same SARS-CoV-2 antigenic protein, emulating a nanobody cocktail. These plant-produced recombinant mosaic VNPs, which are filamentous and flexuous in shape, presenting two different fused proteins on the surface, represent a molecular tool with several potential applications in biotechnology.

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Systemic administration of a viral nanoparticle neoadjuvant prevents lung metastasis development through emergency myelopoiesis

Bourguignon,

Hétu-Arbour,

Charpentier

et al. 2024

OncoImmunology

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Cancer presents a significant public health concern, particularly in the context of metastatic disease. Surgical removal of primary tumors, while essential, can inadvertently heighten the risk of metastasis. Thus, there is a critical need for innovative neoadjuvant therapies capable of curtailing metastatic progression before or immediately following tumor resection. Addressing this imperative, the papaya mosaic virus nanoparticle (PapMV) has demonstrated potent immunostimulatory capabilities against both viruses and tumors, effectively hindering their proliferation. Our study reveals that PapMV exerts a protective effect against lung metastasis when administered systemically prior to tumor implantation or during the early stages of metastasis in various mouse models of cancer. This anti-tumor effect is initiated by the recruitment of myeloid cells in the lungs. These cells adopt a pro-inflammatory profile, secreting cytokines such as IFN-α, thus fostering a tumor microenvironment inhospitable to tumor progression. Crucially, this protective mechanism hinges on the presence of macrophages before treatment. TLR7 and IFN-I signaling pathways also play pivotal roles in this process. Furthermore, our findings demonstrate that PapMV triggers the activation of the bone marrow emergency response, which accounts for the influx of myeloid cells into the lungs. This study unveils a novel aspect of PapMV’s functionality. By bolstering the immune system, PapMV confers robust protection against metastasis at an early stage of disease progression. This discovery holds promise for therapeutic intervention, particularly as a preemptive measure prior to or just after surgical intervention.

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Plant Virus Nanoparticles Combat Cancer

Cited by 4 publications

References 126 publications

Plant Virus Intratumoral Immunotherapy with CPMV and PVX Elicits Durable Antitumor Immunity in a Mouse Model of Diffuse Large B-Cell Lymphoma

Plant Virus Intratumoral Immunotherapy with CPMV and PVX Elicits Durable Antitumor Immunity in a Mouse Model of Diffuse Large B-Cell Lymphoma

Production of Plant Virus-Derived Hybrid Nanoparticles Decorated with Different Nanobodies

Systemic administration of a viral nanoparticle neoadjuvant prevents lung metastasis development through emergency myelopoiesis

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