Slow-Release Formulation of Cowpea Mosaic Virus for In Situ Vaccine Delivery to Treat Ovarian Cancer.

Anna E Czapar,Frank A Veliz,Nicole F Steinmetz,Jonathan K Pokorski,Brylee David B Tiu

doi:10.1002/advs.201700991

Anna E Czapar, Frank A Veliz + Show 3 more

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https://doi.org/10.1002/advs.201700991

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Abstract

The plant viral nanoparticle cowpea mosaic virus (CPMV) is shown to be an effective immunotherapy for ovarian cancer when administered as in situ vaccine weekly, directly into the intraperitoneal (IP) space in mice with disseminated tumors. While the antitumor efficacy is promising, the required frequency of administration may pose challenges for clinical implementation. To overcome this, a slow release formulation is developed. CPMV and polyamidoamine generation 4 dendrimer form aggregates (CPMV‐G4) based on electrostatic interactions and as a function of salt concentration, allowing for tailoring of aggregate size and release of CPMV. The antitumor efficacy of a single administration of CPMV‐G4 is compared to weekly administration of soluble CPMV in a mouse model of peritoneal ovarian cancer and found to be as effective at reducing disease burden as more frequent administrations of soluble CPMV; a single injection of soluble CPMV, does not significantly slow cancer development. The ability of CPMV‐G4 to control tumor growth following a single injection is likely due to the continued presence of CPMV in the IP space leading to prolonged immune stimulation. This enhanced retention of CPMV and its antitumor efficacy demonstrates the potential for viral–dendrimer hybrids to be used for delayed release applications.

Highlights

Title Slow-Release Formulation of Cowpea Mosaic Virus for In Situ Vaccine Delivery to Treat Ovarian Cancer
The antitumor efficacy of a single administration of CPMV-G4 is compared to weekly administration of soluble CPMV in a mouse model of peritoneal ovarian cancer and found to be as effective at reducing disease burden as more frequent administrations of soluble the efficacy of an in situ vaccination strategy using the nanoparticles formed by the plant virus cowpea mosaic virus (CPMV); efficacy was demonstrated in several tumor types, including ovarian
A single administration of the CPMV-G4 hybrid resulted in matched efficacy compared to weekly treatment using the soluble CPMV formulation

Summary

Introduction

Title Slow-Release Formulation of Cowpea Mosaic Virus for In Situ Vaccine Delivery to Treat Ovarian Cancer. The plant viral nanoparticle cowpea mosaic virus (CPMV) is shown to be an chemotherapies are usually initially effective in treating ovarian cancer, the develeffective immunotherapy for ovarian cancer when administered as in situ vaccine opment of platinum resistance often weekly, directly into the intraperitoneal (IP) space in mice with disseminated leads to disease recurrence, making clear tumors. The ability of CPMV-G4 to control tumor growth following a single through direct administration of an injection is likely due to the continued presence of CPMV in the IP space leading to prolonged immune stimulation. This enhanced retention of CPMV and its antitumor efficacy demonstrates the potential for viral–dendrimer hybrids to be used for delayed release applications. While platinum to determine specific antigens for a given malignancy.[7,8]

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