In Situ Vaccination of Tumors Using Plant Viral Nanoparticles

Murray, Abner A.; Sheen, Mee Rie; Veliz, Frank A.; Fiering, Steven; Steinmetz, Nicole F.

doi:10.1007/978-1-4939-9516-5_10

Cited by 15 publications

(15 citation statements)

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“…Soft proteinaceous nanoparticles derived from the capsids of bacteriophages or plants have emerged as promising technologies in imaging , and drug delivery − and as noninfectious models in vaccine development. ,,− In particular, virus-like particles (VLPs)engineered nanostructures that self-assemble from individual coat proteins (CPs) of a virusare structurally similar to their viral analogs but lack the genetic material needed for replication . VLPs can be expressed in a scalable and straightforward fashion in a variety of systems including insect cells, mammalian cells, and bacteria .…”

Section: Introductionmentioning

confidence: 99%

Supramolecular Encapsulation of Small-Ultrared Fluorescent Proteins in Virus-Like Nanoparticles for Noninvasive In Vivo Imaging Agents

et al. 2020

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Icosahedral virus-like particles (VLPs) derived from bacteriophages Qβ and PP7 encapsulating small-ultra red fluorescent protein (smURFP) were produced using a versatile supramolecualr capsid dissassemble-reassemble approach. The generated fluorescent VLPs display identical structural properties to their non-fluorescent analogs. Encapsulated smURFP shows indistinguishable photochemical properties to its unencapsulated counterpart, exhibits outstanding stability towards pH, and produces bright in vitro images following phagocytosis by macrophages. In vivo imaging allows biodistribution to be imaged at different time points. Ex vivo imaging of intravenously administered encapsulated smURFP reveleas localization in the liver and kidneys after 2 h blood circulation and substantial elimination after 16 h of imaging highlighting the potential application of these constructs as non-invasive in vivo imaging agents.

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Section: Introductionmentioning

confidence: 99%

Supramolecular Encapsulation of Small-Ultrared Fluorescent Proteins in Virus-Like Nanoparticles for Noninvasive In Vivo Imaging Agents

et al. 2020

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“…CPMV nanoparticles were prepared as previously described and were verified to have < 50 endotoxin units per mg protein [ 82 ]. CPMV was diluted in PBS to a concentration of 100 µg per 200 µL PBS.…”

Section: Methodsmentioning

confidence: 99%

Remission-Stage Ovarian Cancer Cell Vaccine with Cowpea Mosaic Virus Adjuvant Prevents Tumor Growth

Stump

Mao

et al. 2021

Cancers

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Ovarian cancer is the deadliest gynecological malignancy. Though most patients enter remission following initial interventions, relapse is common and often fatal. Accordingly, there is a substantial need for ovarian cancer therapies that prevent relapse. Following remission generated by surgical debulking and chemotherapy, but prior to relapse, resected and inactivated tumor tissue could be used as a personalized vaccine antigen source. The patient’s own tumor contains relevant antigens and, when combined with the appropriate adjuvant, could generate systemic antitumor immunity to prevent relapse. Here, we model this process in mice to investigate the optimal tumor preparation and vaccine adjuvant. Cowpea mosaic virus (CPMV) has shown remarkable efficacy as an immunostimulatory cancer therapy in ovarian cancer mouse models, so we use CPMV as an adjuvant in a prophylactic vaccine against a murine ovarian cancer model. Compared to its codelivery with tumor antigens prepared in three other ways, we show that CPMV co-delivered with irradiated ovarian cancer cells constitutes an effective prophylactic vaccine against a syngeneic model of ovarian cancer in C57BL/6J mice. Following two vaccinations, 72% of vaccinated mice reject tumor challenges, and all those mice survived subsequent rechallenges, demonstrating immunologic memory formation. This study supports remission-stage vaccines using irradiated patient tumor tissue as a promising option for treating ovarian cancer, and validates CPMV as an antitumor vaccine adjuvant for that purpose.

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“…5 cowpea plants and purified as previously described. 60 Bioconjugation of Cy3 and Cy5 Fluorophores to CPMV External Lysine Residues. The CPMV protein capsid consists of 180 coat proteins upon which surface-exposed lysine side chains are displayed.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Active Microneedle Administration of Plant Virus Nanoparticles for Cancer In Situ Vaccination Improves Immunotherapeutic Efficacy

Boone

Wang

Lopez‐Ramirez

et al. 2020

ACS Appl. Nano Mater.

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The solid tumor microenvironment (TME) poses a significant structural and biochemical barrier to immunotherapeutic agents. To address the limitations of tumor penetration and distribution and to enhance antitumor efficacy of immunotherapeutics, we present here an autonomous active microneedle (MN) system for the direct intratumoral (IT) delivery of a potent immunoadjuvant, cowpea mosaic virus nanoparticles (CPMV), in vivo. In this active delivery system, magnesium (Mg) microparticles embedded into active MNs react with the interstitial fluid in the TME, generating a propulsive force to drive the nanoparticle payload into the tumor. Active delivery of the CPMV payload into B16F10 melanomas in vivo demonstrated substantially more pronounced tumor regression and prolonged survival of tumor-bearing mice compared to that of passive MNs and conventional needle injection. Active MN administration of CPMV also enhanced local innate and systemic adaptive antitumor immunity. Our approach represents an elaboration of conventional CPMV in situ vaccination, highlighting substantial immune-mediated antitumor effects and improved therapeutic efficacy that can be achieved through CPMV in situ vaccination mediated by an active and autonomous delivery system.

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In Situ Vaccination of Tumors Using Plant Viral Nanoparticles

Cited by 15 publications

References 1 publication

Supramolecular Encapsulation of Small-Ultrared Fluorescent Proteins in Virus-Like Nanoparticles for Noninvasive In Vivo Imaging Agents

Supramolecular Encapsulation of Small-Ultrared Fluorescent Proteins in Virus-Like Nanoparticles for Noninvasive In Vivo Imaging Agents

Remission-Stage Ovarian Cancer Cell Vaccine with Cowpea Mosaic Virus Adjuvant Prevents Tumor Growth

Active Microneedle Administration of Plant Virus Nanoparticles for Cancer In Situ Vaccination Improves Immunotherapeutic Efficacy

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