Format

Send to

Choose Destination
Nano Lett. 2017 Jul 12;17(7):4019-4028. doi: 10.1021/acs.nanolett.7b00107. Epub 2017 Jun 26.

Combination of Plant Virus Nanoparticle-Based in Situ Vaccination with Chemotherapy Potentiates Antitumor Response.

Author information

1
Department of Biomedical Engineering, Case Western Reserve University Schools of Medicine and Engineering , 10900 Euclid Avenue, Cleveland, Ohio 44106, United States.
2
Department of Microbiology and Molecular Biology, Case Western Reserve University School of Medicine , 10900 Euclid Avenue, Cleveland, Ohio 44106, United States.
3
Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth , Hanover, New Hampshire 03755, United States.
4
Department of Molecular Biotechnology, RWTH-Aachen University , 52064 Aachen, Germany.
5
Norris Cotton Cancer Center, Lebanon, New Hampshire 03756, United States.
6
Department of Radiology, Case Western Reserve University School of Medicine , 10900 Euclid Avenue, Cleveland, Ohio 44106, United States.
7
Department of Materials Science and Engineering, Case Western Reserve University School of Engineering , 10900 Euclid Avenue, Cleveland, Ohio 44106, United States.
8
Department of Macromolecular Science and Engineering, Case Western Reserve University School of Engineering , 10900 Euclid Ave., Cleveland, Ohio 44106, United States.
9
Division of General Medical Sciences-Oncology, Case Western Reserve University , 10900 Euclid Avenue, Cleveland, Ohio 44106, United States.

Abstract

Immunotherapeutics are gaining more traction in the armamentarium used to combat cancer. Specifically, in situ vaccination strategies have gained interest because of their ability to alter the tumor microenvironment to an antitumor state. Herein, we investigate whether flexuous plant virus-based nanoparticles formed by the potato virus X (PVX) can be used as an immunotherapeutic for in situ vaccine monotherapy. We further developed dual chemo-immunotherapeutics by incorporating doxorubicin (DOX) into PVX yielding a dual-functional nanoparticle (PVX-DOX) or by coadministration of the two therapeutic regimes, PVX immunotherapy and DOX chemotherapy (PVX+DOX). In the context of B16F10 melanoma, PVX was able to elicit delayed tumor progression when administered as an intratumoral in situ vaccine. Furthermore, the coadministration of DOX via PVX+DOX enhanced the response of the PVX monotherapy through increased survival, which was also represented in the enhanced antitumor cytokine/chemokine profile stimulated by PVX+DOX when compared to PVX or DOX alone. Importantly, coadministered PVX+DOX was better for in situ vaccination than PVX loaded with DOX (PVX-DOX). Whereas the nanomedicine field strives to design multifunctional nanoparticles that integrate several functions and therapeutic regimens into a single nanoparticle, our data suggest a paradigm shift; some therapeutics may need to be administered separately to synergize and achieve the most potent therapeutic outcome. Altogether, our studies show that development of plant viral nanoparticles for in situ vaccines for treatment is a possibility, and dual mechanistic therapeutics can increase efficacy. Nonetheless, combining immunotherapeutics with cytolytic chemotherapy requires detailed investigation to inform optimal integration of cytolytic and immunotherapies and maximize synergy and efficacy.

KEYWORDS:

Plant virus nanoparticle; cancer; chemotherapy; cowpea mosaic virus; immunotherapy; in situ vaccination; melanoma; potato virus X

Supplemental Content

Full text links

Icon for American Chemical Society Icon for PubMed Central
Loading ...
Support Center